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EP-4291170-B1 - USE OF CANNABIDIVARIN IN THE TREATMENT OF SEIZURES ASSOCIATED WITH CANINE EPILEPSY

EP4291170B1EP 4291170 B1EP4291170 B1EP 4291170B1EP-4291170-B1

Inventors

  • TSE, Karen Ka-Yen

Dates

Publication Date
20260513
Application Date
20220127

Claims (10)

  1. A cannabidivarin (CBDV) preparation for use in the treatment of seizures associated with canine epilepsy, wherein the dose of CBDV is between 75 mg/kg/day and 125 mg/kg/day, wherein the CBDV preparation comprises greater than 95% (w/w) CBDV and not more than 1.5% (w/w) tetrahydrocannabinol (THC).
  2. A CBDV preparation for use according to claim 1, wherein the seizures associated with epilepsy are tonic, clonic, tonic-clonic, atonic, myoclonic, absence, focal seizures without impairment, focal seizures with impairment, and focal seizures with secondary generalisation.
  3. A CBDV preparation for use according to any of the preceding claims, wherein the CBDV preparation comprises greater than or equal to 95% (w/w) CBDV and less than or equal to 5% (w/w) other cannabinoids, wherein the less than or equal to 5% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); tetrahydrocannabivarin (THCV); cannabidiol-C1 (CBD-C1); cannabidiol (CBD); cannabidivarin acid (CBDVA) and cannabidiol-C4 (CBD-C4).
  4. A CBDV preparation for use according to any of the preceding claims, wherein the CBDV preparation is used in combination with one or more concomitant anti-epileptic drugs (AED).
  5. A CBDV preparation for use according to any of the preceding claims, wherein the CBDV is present is isolated from cannabis plant material.
  6. A CBDV preparation for use according to any of the preceding claims, wherein at least a portion of at least one of the cannabinoids present in the CBDV preparation is isolated from cannabis plant material.
  7. A CBDV preparation for use according to claims 1 to 4, wherein the CBDV is present as a synthetic preparation.
  8. A CBDV preparation for use according to claim 7, wherein at least a portion of at least one of the cannabinoids present in the CBDV preparation is prepared synthetically.
  9. A CBDV preparation for use according to any of claims 1 to 8, wherein the dose of CBDV is 100 mg/kg/day.
  10. A CBDV preparation for use according to claim 9, wherein the preparation is administered orally.

Description

FIELD OF THE INVENTION The present invention relates to the use of cannabidivarin (CBDV) for the treatment of seizures associated with canine epilepsy. The CBDV used is in the form of a highly purified extract of cannabis such that the CBDV is present at greater than 95% of the total extract (w/w) and the cannabinoid tetrahydrocannabinol (THC) has been substantially removed, to a level of not more than 1.5% (w/w). Preferably the CBDV used is in the form of a botanically derived purified CBDV which comprises greater than or equal to 95% (w/w) CBDV and less than or equal to 5% (w/w) other cannabinoids, wherein the less than or equal to 5% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); tetrahydrocannabivarin (THCV); cannabidiol-C1 (CBD-C1); cannabidiol (CBD); cannabidivarin acid (CBDVA) and cannabidiol-C4 (CBD-C4). Alternatively, a synthetically produced CBDV is used. BACKGROUND TO THE INVENTION Epilepsy is reported to be the most common neurological disorder in dogs and has been estimated to affect approximately 0.75% of the canine population.1 A limited number of existing anti-epileptic drugs (AEDs) have been approved for the treatment of epilepsy in dogs worldwide.2 The 2015 American College of Veterinary Internal Medicine consensus statement on seizure management in dogs indicates that anticonvulsant treatment should be initiated with either one of the AEDs phenobarbital or potassium bromide. However, a 2008 study found that treatment of canine epilepsy by a combination of the two AEDs is ineffective in reducing seizures in about 20% to 30% of dogs.3 Increasing dosage may improve seizure control but due to side effects and toxicity (polyuria/polydipsia, polyphagia, ataxia, lethargy and hepatoxicity), this is not possible. The ineffectiveness and adverse effects of these drugs have led to the search for more effective treatments. A number of different underlying diseases and factors can cause seizures leading to epilepsy in dogs. The condition can be inherited (genetic or idiopathic epilepsy), caused by structural problems in the brain (structural epilepsy), or stem from an unknown cause (epilepsy of unknown cause). The main symptom of epilepsy is repeated seizures. In order to determine the type of seizures, clinical observations and electroencephalography (EEG) tests are conducted and the type(s) of seizures in humans can be classified according to the International League Against Epilepsy (ILEA) classification. Although such classification systems exist for human seizures, there is not yet a widely accepted classification system available for seizures in dogs. Recently, the International Veterinary Epilepsy Task Force proposed a classification scheme for veterinary seizures,4 similar to the current human ILAE classification system. Focal epileptic seizures originate in a discrete area of the brain and are characterized by signs that affect a single side or specific part of the body. Focal epileptic seizures can present in the following ways in dogs: i) motor (episodic focal motor phenomena e.g. facial twitches, repeated jerking head movements, rhythmic blinking, twitching of facial musculature or repeated rhythmic jerks of one extremity); ii) autonomic (parasympathetic and epigastric components e.g. dilated pupils, hypersalivation or vomiting); and iii) behavioural (short lasting episodic change in behaviour e.g. anxiousness, restlessnesss, unexplainable fear reactions or abnormal attention seeking/'clinging' to the owner.) Generalised epileptic seizures are characterised by bilateral involvement of both sides of the body as both cerebral hemispheres are involved. In dogs and cats, generalized epileptic seizures predominantly present as tonic, clonic or tonic-clonic epileptic seizures with possible loss of consciousness. Furthermore salivation, urination and/or defecation often occur. Animals may also experience other generalised convulsive epileptic seizures such as myoclonic seizures (jerking movements usually affecting both sides of the body). Non-convulsive generalized epileptic seizures experienced by animals include atonic seizures, whereby the sudden and general loss of muscle tone causes the animal to collapse. Focal epileptic seizures can spread from initial regional cerebral involvement to bilateral cerebral involvement (focal epileptic seizures evolving into generalised epileptic seizures). The seizure starts with regional motor, autonomic and/or behavioural signs and then is rapidly followed by a convulsive stage with bilateral tonic, clonic or tonic-clonic activity and loss of consciousness. This is the most common seizure type observed in the dog. The onset of the focal epileptic seizure is often very short (seconds to minutes) after which follows the secondary generalisation with convulsions. The focal epileptic seizure onset may be difficult to detect due to its brief nature. Cannabidiol (CBD), a non-psychoactive derivative from the cannabis plant, has demo