Fireworks anxiety in dogs and cats:
the HPA axis, gut-brain axis and why starting early makes all the difference

Fear of fireworks is rarely a behavioral problem alone. Behind the panic lies a physiologically disturbed system: an overactive HPA axis, a disturbed neurotransmitter balance and sometimes a gut-brain axis that amplifies the stress response from within. How that mechanism works and why supplements only really help if you start on time.

By Stefan Veenstra DVM

What happens in the nervous system with fear of fireworks

If a dog panics at fireworks, it is not irrational. It is a programmed survival response to an abrupt, loud, unpredictable sound that in the evolutionary context always meant danger. The amygdala, the brain’s fear center, processes the sound signal and activates the hypothalamus within milliseconds. This sends the signal via the HPA axis to the adrenal glands, which emit cortisol and adrenaline. The body is ready for flight or fight.

In most dogs, this would be a short-term acute response that normalizes after the danger. In chronically anxious animals, the feedback mechanism is damaged. The hippocampus, which normally regulates cortisol decline via negative feedback, has become less sensitive to cortisol signals in chronically stressed animals. The system stays on. Cortisol levels remain elevated, the amygdala is chronically sensitized and the threshold for a panic response continues to drop. Every year, fireworks are a little worse than the year before.

Sedatives: they dampen consciousness but not fear

A common mistake with fireworks anxiety is the use of sedatives such as acepromazine. Acepromazine doses the animal’s motor ability but leaves the fear intact. The animal can no longer react but experiences the fear completely. Research has shown that animals under acepromazine have similar or even higher cortisol responses to fireworks than without sedation. Sedation for fear of fireworks is therefore ethically problematic and mechanistically ineffective.

The gut-brain axis: why the gut should be treated for severe anxiety

The gut-brain axis is a bidirectional communication pathway between the enteric nervous system and the central nervous system through the vagus nerve, immune system, and endocrine pathway. 90% of the serotonin in the body is produced in the gut by enterochromaffin cells whose activity is directly dependent on the microbiome.

A dysbiotic microbiome produces fewer serotonin precursors, more pro-inflammatory metabolites, and increased LPS production that causes neuroinflammation via leaky gut. The result is an animal that is physiologically less able to calm down, not because it is poorly trained but because the neurochemical basis for calming is missing.

In animals with severe fear of fireworks, the intestine is almost always a relevant point of attention. Chronic stress increases gut permeability via cortisol induction, which exacerbates dysbiosis, which increases stress reactivity. A vicious circle that is only broken by structurally repairing the intestine, and that takes four to six months.

Roller oil and diffuser oil: mechanism of action and safety by product

The olfactory system is the fastest sensory system for emotional processing in mammals. The olfactory bulb has a direct connection to the amygdala and hippocampus without the intermediate step of the thalamus that other sensory stimuli have to go through. Fragrances can therefore influence the emotional state faster and more directly than visual or auditory stimuli.

The NGD Care Firework Support Essential oil Roller contains cedarwood, patchouli, lavender, frankincense and cypress. Lavender (linalool and linalyl acetate) has the strongest veterinary evidence for calming effects in dogs: one study showed that environmental exposure to lavender scent resulted in more resting and less vocalizing during car rides. Frankincense and cedarwood are considered by multiple veterinary aromatherapists to be relatively safe oils that modulate the limbic system through the olfactory pathway.

The Roller Oil is applied to the collar, the flight area or the sleeping place. The NGD Care Diffuser Oil also contains ylang ylang, which provides a deeper relaxing effect in dogs via the limbic system.

Cat safety: two clear guidelines

Roller oil in cats: distance only. The oils in the Roller oil (cedarwood, frankincense, lavender) are considered relatively less toxic to cats by multiple sources. However, the following applies to all essential oils in cats: never apply directly to the coat. Cats lick themselves intensively and thus absorb essential oils internally, which can become toxic due to their limited liver metabolization (lack of glucuronosyltransferase). Only use the roller oil on the sleeping place or basket at a distance from the animal.

Diffuser oil with ylang ylang: not suitable for cats. Ylang ylang is explicitly on the list of essential oils that are harmful to cats, including through inhalation. The diffuser oil is only suitable for use on dogs in well-ventilated areas where the dog can run away freely.

Ashwagandha, Rhodiola and Relax Support: Structural and Direct

Ashwagandha (Withania somnifera) modulates the HPA axis through two mechanisms. Withanolides, the active ingredients, activate GABA-A receptors in the hypothalamus, reducing CRH secretion. At the same time, ashwagandha inhibits enzymatic cortisol production in the adrenal cortex via inhibition of steroidogenic enzymes. The effect builds up over two to four weeks. An RCT in anxious dogs (Dramard et al., 2023) showed significant reduction in anxiety scores after eight weeks of ashwagandha supplementation.

This is exactly why starting two months in advance is necessary for the Adaptogen Complex. Ashwagandha is not an acute-acting drug. It works by structurally rebalancing the stress system. Rhodiola modulates the energy management of the adrenal gland via AMPK activation and protects adrenal gland tissue from exhaustion in chronic stress.

Relax Support complements the structural action of the adaptogens with direct neurotransmitter support. L-theanine modulates alpha brainwave activity within thirty to sixty minutes via GABA-A and NMDA receptors and gives a state of relaxed alertness without sedation. L-tryptophan provides the direct precursor for serotonin synthesis via the 5-HTP pathway. Magnesium modulates NMDA receptors and supports GABA synthesis as a cofactor. Relax Support is therefore the fastest working supplement in the extensive package: it works both in the two-month start-up period and acutely on the evening of New Year’s Eve itself, in combination with CBD oil.

CBD oil

CBD modulates the fear response via CB1 receptors in the limbic system and via 5-HT1A serotonin receptors. The effect occurs within thirty to sixty minutes after administration and makes CBD, in addition to Relax support, the only supplement in this protocol that is also useful as an extra dose on the evening of New Year’s Eve itself. The structural build-up via ashwagandha and Myco Adaptogen lowers the baseline threshold; CBD lowers the acute reaction in the moment.

A 2023 study in Frontiers in Veterinary Science confirmed anxiolytic effects of CBD in dogs in multiple stress-inducing situations. CBD does not have a sedative effect at therapeutic doses: the animal remains alert but reacts less strongly to stress stimuli.

The protocol in time: when to start with what

Regular medication for fear of fireworks: pros and cons

Three drugs are currently most commonly prescribed for fireworks anxiety in dogs in the Netherlands: Pexion (imepitoin), Sileo (dexmedetomidine) and Tessie (trazodone). All three are legitimate and effective in the right context. They also each have their own mechanism, limitations and side effects that are relevant to the choice.

Pexion (imepitoin) — GABA partial agonist

Pexion contains imepitoin, a low-affine partial agonist at the benzodiazepine binding site at the GABA-A receptor. It acts anxiolytically without the complete sedation of classical benzodiazepines as diazepam. Imepitoin is prescribed in Europe for the treatment of epilepsy in dogs and additionally for noise aversion. A double-blind, placebo-controlled RCT in 238 dogs on New Year’s Eve showed significant reductions in anxiety behaviors compared to placebo. Advantage: no sedation, no tolerance build-up with repeated use in contrast to classic benzodiazepines, easy to administer orally twice a day.

Pexion should be launched two days before the expected sound event and passed three days. That requires planning ahead. Side effects include ataxia and increased appetite at higher doses (30 mg/kg twice daily). A specific point of attention: as a partial benzodiazepine receptor agonist, Pexion can induce disinhibition of fear-based behavior in some animals, leading to increased aggression in rare cases. Close monitoring by the owner is recommended, particularly in animals with a history of fear-related aggression.

Combination with the protocol: Pexion works via GABA, the supplement protocol works via HPA axis, gut-brain axis and the endocannabinoid system. The mechanisms do not overlap significantly: combining is possible and can be useful in severe cases. Consultation with the veterinarian is required.

Sileo (dexmedetomidine)—alpha-2-adrenergic agonist

Sileo is an oromucosal gel that delivers dexmedetomidine via absorption through the oral mucosa between cheek and gums. Dexmedetomidine is an alpha-2-adrenergic agonist that modulates the stress response through the locus coeruleus in the brainstem, the fear and memory center for stress responses. Sileo is the only FDA-approved agent specifically for sound aversion in dogs and has the fastest efficacy profile of the three: effect within thirty minutes of administration. This makes it suitable for unexpected sound events where no advance planning is possible.

At therapeutic doses, the effect is anxiolytic without heavy sedation: dogs remain alert and interactive. Some animals experience slight drowsiness. Known side effect is pale mucous membranes due to vasoconstriction, which is not clinically problematic in most dogs but can seem concerning to owners. Sileo is contraindicated in heart disease, liver disease and kidney disease. Repeated dosing is possible with a minimum of two hours between doses.

Combination with the protocol: Sileo is acutely effective and complementary to the preventive supplement protocol. The protocol lowers the base threshold via HPA-axis modulation; Sileo lowers the acute response in the moment. This is mechanistically the most logical combination of regular and integrative. Consultation with veterinarian required; Combination with other sedatives or anxiolytics should be handled with caution.

Tessie (trazodone) — serotonin antagonist and reuptake inhibitor

Trazodone is a SARI antidepressant (serotonin antagonist and reuptake inhibitor) that has been used in human medicine for decades and is widely used off-label in veterinary behavioral medicine. Tessie is the Dutch veterinary brand name. Trazodone inhibits the reuptake of serotonin while blocking specific serotonin receptors (5-HT2A), which gives an anxiolytic and mild sedative effect. It works within one to two hours after administration, and the effect lasts for six to twelve hours.

Trazodone is not specifically registered for sound aversion but is widely and effectively used for situational anxiety, fear of fireworks, separation anxiety and stressful situations such as veterinarian or surgery recovery. It can be given daily or situationally. Side effects are mild: most common are gastrointestinal complaints, ataxia at higher doses and sometimes sedation. A rare but serious side effect is serotonin syndrome, especially when combined with other serotonergic drugs such as MAOIs or certain other antidepressants. When combined with the supplement protocol, it is relevant that L-tryptophan in Relax Support is a serotonin precursor: at high doses of trazodone, this is not an advised combination.

Combination with the protocol: trazodone and the supplement protocol work on partially overlapping pathways (serotonin system). In case of mild anxiety, the supplement protocol is an alternative with no side effects; In severe anxiety, trazodone may be more effective. Consultation about combination with L-tryptophan-containing supplements is recommended.

Fluoxetine (Reconcile / Prozac) — SSRI for long-term use

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) known in human medicine as Prozac and in veterinary medicine under the brand name Reconcile. In the Netherlands, it is prescribed off-label. Fluoxetine blocks the reuptake of serotonin in the synapse, causing serotonin levels to rise structurally. It is best suited for chronic, daily anxiety problems and structural behavioral problems such as separation anxiety, generalized anxiety disorders and chronic noise phobia as an underlying problem.

The basic difference with trazodone is the time scale. Fluoxetine has a lead time of two to four weeks before an effect is noticeable. That makes it not suitable as the only remedy for fear of fireworks: those who start on December 28 have no effect on New Year’s Eve. Fluoxetine is useful as a daily basic medication for dogs with chronic anxiety where fireworks are one of the many triggers. In that case, trazodone or Sileo can be added situationally.

Combination with the supplement protocol: fluoxetine and the supplement protocol partially overlap via the serotonin pathway. L-tryptophan in Relax Support is a serotonin precursor: at high doses of fluoxetine, caution is advisable and the combination should be discussed with the treating veterinarian to avoid serotonin syndrome. Fluoxetine and trazodone together increase the risk of serotonin syndrome; The same applies in principle to combination with serotonergic supplements at high doses.

The combination with behavioural therapy

Supplements can make the nervous system more receptive to learning but do not replace behavioral therapy guidance for severe anxiety. Desensitization (gradual exposure to firework sounds at low volume) and counterconditioning (building positive associations with the sound) are the most evidence-based behavioral interventions in noise phobia. The combination of a neurochemically balanced nervous system through the supplement protocol and systematic behavioral therapy gives the best results.

This article is educational in nature and does not replace veterinary consultation or behavioural counselling. In case of severe fear or aggression, always call in a certified behavioural therapist. Use aromatherapy in cats only with extra caution.

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