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JSM Veterinary Medicine and Research

NegEnt Micellar CBD for Canine Anxiety and Stress Related Disorders: Scientific Rationale and Clinical Case Report

[ ISSN : 2689-1565 ]

Abstract Citation INTRODUCTION METHODS COMPOSITION OF NEGENT DROPS: RESULTS DISCUSSION CONFLICT OF INTEREST STATEMENT ETHICAL STATEMENT REFERENCES
Details

Received: 21-Jul-2026

Accepted: 04-Sep-2026

Published: 05-Sep-2026

Scrimali T* and Messina F*

DISFOR Department, University of Catania, Italy

Corresponding Author:

Scrimali T, DISFOR Department, University of Catania, Italy

Keywords

NegEnt Micellar CBD; Canine Anxiety; Terpenolol; CB1 Allosteric Modulation; Quantum Pharmacodynamics.

Abstract

Canine anxiety is a widespread behavioural condition that compromises animal welfare and increases the risk of stress related behavioural dysregulation. Severe anxiety disrupts cognitive processing, sleep regulation, and social functioning, often requiring pharmacological support to enable behavioural rehabilitation. This case report describes the clinical response of a 4-year-old Italian Volpino dog with chronic anxiety, hyperarousal, and stress-related dysregulation treated with a micellar CBD formulation (NegEnt). The treatment produced rapid improvements in sleep continuity, arousal modulation, social behaviour, and impulse control without cognitive or motor impairment. Furthermore, a planned temporary discontinuation demonstrated the absence of withdrawal or rebound effects, followed by sustained long-term efficacy over a two-month maintenance period. These observations suggest that micellar CBD may facilitate a “window of cognitive plasticity” that supports behavioural therapy. Controlled studies are required to confirm these preliminary findings.

Citation

Scrimali T, Messina F, (2026) NegEnt Micellar CBD for Canine Anxiety and Stress-Related Disorders: Scientific Rationale and Clinical Case Report JSM Vet Med Res 5(1): 3.

INTRODUCTION

Anxiety and stress-related behavioural disorders in dogs represent a major challenge in veterinary behavioural medicine. Conventional pharmacological options—primarily benzodiazepines and neuroleptics—show significant limitations in chronic emotional disorders. Benzodiazepines may induce paradoxical excitement, disinhibited aggression, and impaired learning [1,2]. Neuroleptics suppress behavioural output without modulating underlying emotional dysregulation and may cause dysphoria, motor rigidity, and cognitive dulling [3].

Cannabidiol (CBD) has emerged as a promising option for emotional disorders in dogs. Pharmacokinetic studies indicate that CBD is well tolerated [4], and clinical observations in epileptic dogs show reductions in hyperarousal and stress-related behaviours [5]. A large survey of U.S. veterinarians reported that CBD is perceived as helpful for anxiety and emotional dysregulation [6].

NegEnt contains Terpenolol, a patented CBD-derived, micellar molecule; the proposed mechanisms of action, although supported by the CBD literature, must be specifically confirmed for Terpenolol, and further research to that end is currently underway, even though some preliminary data exist [7].

a Class I Medical Device, based on a physical and reversible mechanism of action, consistent with the European regulatory definition of medical devices, which requires non-pharmacological, non-immunological, and non-metabolic activity (Directive 93/42/EEC; Regulation (EU) 2017/745).

The theoretical rationale of NegEnt relies on a quantum-physical reversible mechanism, in which micellized terpenolol modulates CB1 receptor conformational states through shifts in electronic energy, molecular resonance, and supramolecular dynamics. This approach aligns with the scientific framework describing medical devices acting through physical mechanisms, where therapeutic activity emerges from physical interactions (adsorption, modulation of molecular energy states, supramolecular structuring) rather than classical pharmacological receptor binding [8].

Case Description

Leo, a 4-year-old Italian Volpino, was adopted at two years of age and immediately displayed separation anxiety, object possessiveness, and heightened reactivity. At age three, his symptoms escalated into episodes of affective aggression triggered by accidental painful stimuli (e.g., stepping on a paw). His triggers included strangers approaching, loud noises, sudden movements, and proximity to his toys.

Daily signs of distress included growling, rigid posture, ears pulled back, fixed gaze, repeated yawning, and continuous lip-licking. Lip-licking is recognised as a parasympathetic self-soothing behaviour elicited by negative emotional stimuli [9-11]. Leo’s hypervigilance prevented normal sleep; he woke at minimal noises and vocalised repeatedly, generating significant emotional and logistical strain for caregivers.

In severe anxiety, neurobiological stimulation surpasses the system’s plasticity threshold, leading to reactive allostasis, where cortical computational systems no longer process environmental stimuli. This state prevents the formation of new positive associations, making behavioural rehabilitation ineffective without pharmacological modulation.

METHODS

Leo received five drops of NegEnt Micellar CBD three times daily (total: 15 drops/day). Each drop contains 10 mg of micellized terpenolol, resulting in a daily dose of 150 mg, equivalent to 15 mg/kg/day for a 10 kg dog. The approximate volume per drop is 0.05 mL, for a total daily volume of 0.75 mL.

To evaluate potential withdrawal effects or rebound phenomena, a planned 2-day treatment discontinuation was implemented after the first week of administration. Following this brief experimental pause, the treatment was promptly resumed and maintained for a total duration of two months, and it is currently ongoing.

COMPOSITION OF NEGENT DROPS:

• Micellized terpenolol (CBD micellar form): 10 mg per drop

• Hydrophilic micelles (non-ionic pharmaceutical-grade surfactants)

• Terpenic carrier matrix

• Purified water

• CE-approved preservative for medical devices

• THC: not present

No other pharmacological agents were used during the observation period. Behavioural changes were monitored daily by caregivers.

RESULTS

Sleep Restoration

Within days, Leo began sleeping for extended periods in relaxed postures, with near-complete disappearance of nocturnal vocalisations.

Morning Arousal Regulation

Stress-related yawning and agitation upon waking were replaced by calm behaviour and a relaxed facial expression.

Reduction of Stress-Related Reactivity

During the initial week of treatment, no episodes of intra-domestic aggression or biting occurred. Possessiveness and hyperactivity decreased markedly.

Improved Social Behaviour

During walks, anxious barking toward conspecifics was replaced by curious and positive interest.

Impulse Control, Absence of Rebound, and Long-Term Follow-Up

The day after the planned 2-day treatment discontinuation, Leo encountered his primary trigger (accidental paw pressure). He growled as a warning but did not escalate to biting, suggesting an increased latency between stimulus and reaction, as well as a retention of the therapeutic benefit. No signs of withdrawal, distress, or rebound anxiety were observed during the 48-hour suspension. Following the resumption of the protocol, the treatment was extended for two months and is still active at the time of writing. Over this extended period, Leo showed stable behavioural consolidation, sustained improvement in sleep quality, and a persistent reduction in hyperarousal, with no documentation of adverse side effects or diminished efficacy (tolerance).

Cognitive and Motor Integrity

No sedation, confusion, or motor impairment was observed. Leo remained alert, coordinated, and capable of emotional modulation (Table 1).

Table 1. A synopsis of the clinical behavioural parameters before and after micellar CBD (NegEnt) administration

Behavioral Domain

Baseline (Before Treatment)

First Week Evaluation

Long-Term Follow-Up

(2 Months)

Sleep Quality

Hypervigilance, frequent waking at minimal noises,

nocturnal vocalisations.

Extended sleep periods, relaxed postures, near-complete disappearance of vocalisations.

Stable sleep consolidation, persistent absence of nocturnal distress.

Morning Arousal

Stress-related yawning and Acute agitation upon waking.

Calm behaviour and Relaxed Facial expression upon

waking.

Sustained morning Emotional regulation.

Intra-domestic Reactivity

High reactivity, object possessiveness, episodes of affective aggression (biting triggers).

Marked decrease in possessiveness and hyperactivity; zero aggression/ biting episodes.

Continuous behavioural stability; zero recurrence of biting episodes.

Social Behaviour (Walks)

Anxious barking toward

conspecifics.

Anxious barking replaced by curious

and positive interest.

Consolidated positive social

interaction with other dogs.

Impulse Control

Low latency between trigger (e.g., accidental pain) and aggressive reaction.

Increased latency (warning growl without escalating to biting).

Maintained impulse control; no rebound effects observed.

Cognitive & Motor Status

Chronic emotional dysregulation, high distress.

Alert, coordinated, capable of emotional modulation (no sedation)

Persistent cognitive and motor integrity; excellent tolerability.

DISCUSSION

The clinical improvements observed in this case are consistent with emerging evidence supporting CBD as a promising anxiolytic agent in dogs. Unlike benzodiazepines-which may produce paradoxical agitation, disinhibited aggression, and impaired learning—CBD exerts multimodal emotional regulation without compromising cognition or motor coordination [1,2]. Neuroleptics, while capable of suppressing overt behavioural responses, do not address underlying emotional dysregulation and may cause dysphoria or cognitive dulling [3].

Micellar terpenolol CBD offers additional advantages due to its supramolecular structure. Enhanced hydro solubility and bypass of first pass metabolism allow rapid absorption at low doses. More importantly, terpenolol appears to modulate CB1 receptors through quantistic allosteric mechanisms, altering receptor conformational energy states and electron-transfer coefficients. This reversible physical mechanism is coherent with the regulatory classification of NegEnt as a Class I Medical Device, where therapeutic action is attributed to physical interactions rather than pharmacological receptor occupation [8].

Notably, the 2-day experimental discontinuation highlighted the absence of rebound anxiety or withdrawal symptoms, which are common limitations of conventional psychotropic drugs. Furthermore, the excellent safety and tolerability profile observed over the subsequent two months of continuous administration underscores the potential of micellar terpenolol CBD as a viable, long-term therapeutic tool.

Notably, the 2-day experimental discontinuation highlighted the absence of rebound anxiety or withdrawal symptoms, which are common limitations of conventional psychotropic drugs. Furthermore, the excellent safety and tolerability profile observed over the subsequent two months of continuous administration underscores the potential of micellar terpenolol CBD as a viable, long-term therapeutic tool.

CONFLICT OF INTEREST STATEMENT

The Authors declare that they have no conflicts of interest related to the conduct of this research. NegEnt Drops were purchased independently and at the dog owner’s personal expense. No funding, sponsorship, or commercial support was received.

ETHICAL STATEMENT

The study adhered to the ethical principles of the Declaration of Helsinki, adapted for non-invasive veterinary behavioural research. No experimental protocols, laboratory procedures, or induced stimuli were applied. The intervention consisted solely of a commercially available Class I Medical Device (NegEnt Drops), purchased at the owner’s expense, administered within routine domestic care. All observations were naturalistic, and informed consent for data collection and publication was obtained from the owner. The report complies with European and Italian guidelines for ethical research involving companion animals.

REFERENCES

1. Overall KL. Manual of clinical behavioural medicine for Dogs and Cats. Elsevier. 2013.

2. Crowell-Davis SL, Murray T. Veterinary Psychopharmacology. Blackwell Publishing. 2006.

3. Landsberg G, Hunthausen W, Ackerman L. Behaviour problems of the Dog and Cat. Saunders Elsevier. 2012.

4. 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; 9: 832.

5. McGrath S, Bartner LR, Rao S, Packer RA, Gustafson DL. Randomized blinded controlled clinical trial to assess the effect of oral cannabidiol administration in addition to conventional antiepileptic treatment on seizure frequency in dogs with intractable idiopathic epilepsy. J Am Vet Med Assoc. 2019; 254: 1301-1308.

6. 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; 5: 338.

7. Scrimali T. Terpenolol: A Novel Hydrophilic CBD-Derived Compound for Pharmaceutical, Nutraceutical, Cosmeceutical, and Functional Food Applications. 2026.

8. Martini M, Ravasio A. Medical devices acting through physical mechanisms: Regulatory and scientific framework. Journal of Applied Biomedical Science, 2020; 8: 45-52.

9. Albuquerque N, Guo K, Wilkinson A, Resende B, Mills DS. Mouth-licking by dogs as a response to emotional stimuli. Behav Processes. 2018; 146: 42-45.

10. d’Ingeo S, Iarussi F, De Monte V, Siniscalchi M, Minunno M, Quaranta A. Emotions and Dog Bites: Could predatory attacks be triggered by emotional states? Animals (Basel). 2021; 11: 2907.

11. Tiira K, Sulkama S, Lohi H. Prevalence, comorbidity, and behavioral variation in canine anxiety. Journal of Veterinary Behavior, 2016; 16: 36-44.

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