WO2022017957A1 - Utilisation de cannabidiol dans le traitement de crises associées à un accident vasculaire cérébral ou à une hémorragie cérébrale - Google Patents

Utilisation de cannabidiol dans le traitement de crises associées à un accident vasculaire cérébral ou à une hémorragie cérébrale Download PDF

Info

Publication number
WO2022017957A1
WO2022017957A1 PCT/EP2021/069898 EP2021069898W WO2022017957A1 WO 2022017957 A1 WO2022017957 A1 WO 2022017957A1 EP 2021069898 W EP2021069898 W EP 2021069898W WO 2022017957 A1 WO2022017957 A1 WO 2022017957A1
Authority
WO
WIPO (PCT)
Prior art keywords
cbd
preparation
seizures
use according
thc
Prior art date
Application number
PCT/EP2021/069898
Other languages
English (en)
Inventor
Daniel Adam CHECKETTS
Kevin James CRAIG
Original Assignee
GW Research Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by GW Research Limited filed Critical GW Research Limited
Publication of WO2022017957A1 publication Critical patent/WO2022017957A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca

Definitions

  • the present invention relates to the use of cannabidiol (CBD) for the treatment of seizures associated with stroke or brain haemorrhage.
  • CBD cannabidiol
  • the types of seizures include tonic, tonic-clonic, atonic, myoclonic, absence, focal seizures without impairment, focal seizures with impairment and focal seizures with secondary generalisation.
  • the dose of CBD is between 5 mg/kg/day to 50 mg/kg/day.
  • the CBD used is in the form of a highly purified extract of cannabis such that the CBD 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 0.15% (w/w).
  • the CBD used is in the form of a botanically derived purified CBD which comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids. More preferably the other cannabinoids present are THC at a concentration of less than or equal to 0.1% (w/w); CBD-C1 at a concentration of less than or equal to 0.15% (w/w); CBDV at a concentration of less than or equal to 0.8% (w/w); and CBD-C4 at a concentration of less than or equal to 0.4% (w/w).
  • the botanically derived purified CBD preferably also comprises a mixture of both trans-THC and cis-THC. Alternatively, a synthetically produced CBD is used.
  • the other cannabinoids present are THC at a concentration of about 0.01% to about 0.1% (w/w); CBD-C1 at a concentration of about 0.1% to about 0.15% (w/w); CBDV at a concentration of about 0.2% to about 0.8% (w/w); and CBD-C4 at a concentration of about 0.3% to about 0.4% (w/w).
  • THC is present at a concentration of about 0.02% to about 0.05% (w/w).
  • the CBD may be formulated for administration separately, sequentially or simultaneously with one or more AED or the combination may be provided in a single dosage form.
  • Epilepsy occurs in approximately 1% of the population worldwide, (Thurman et al., 2011) of which 70% are able to adequately control their symptoms with the available existing anti-epileptic drugs (AED). However, 30% of this patient group, (Eadie etal., 2012), are unable to obtain seizure freedom from the AED that are available and as such are termed as suffering from intractable or “treatment-resistant epilepsy” (TRE).
  • TRE treatment-resistant epilepsy
  • Intractable or treatment-resistant epilepsy was defined in 2009 by the International League against Epilepsy (I LAE) as “failure of adequate trials of two tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom ” (Kwan et al., 2009).
  • Childhood epilepsy is a relatively common neurological disorder in children and young adults with a prevalence of approximately 700 per 100,000. This is twice the number of epileptic adults per population.
  • the main symptom of epilepsy is repeated seizures.
  • Clinical observations and electroencephalography (EEG) tests are conducted and the type(s) of seizures are classified according to the ILEA classification.
  • Generalized seizures where the seizure arises within and rapidly engages bilaterally distributed networks, can be split into six subtypes: tonic-clonic (grand mal) seizures; absence (petit mal) seizures; clonic seizures; tonic seizures; atonic seizures and myoclonic seizures.
  • Focal (partial) seizures where the seizure originates within networks limited to only one hemisphere, are also split into sub-categories.
  • the seizure is characterized according to one or more features of the seizure, including aura, motor, autonomic and awareness / responsiveness.
  • a seizure begins as a localized seizure and rapidly evolves to be distributed within bilateral networks this seizure is known as a bilateral convulsive seizure, which is the proposed terminology to replace secondary generalized seizures (generalized seizures that have evolved from focal seizures and are no longer remain localized).
  • Focal seizures where the subject’s awareness / responsiveness is altered are referred to as focal seizures with impairment and focal seizures where the awareness or responsiveness of the subject is not impaired are referred to as focal seizures without impairment.
  • An ischaemic stroke is the most common type of stroke and is caused by a blood clot blocking the flow of blood and oxygen to the brain.
  • a haemorrhagic stroke occurs when a blood vessel inside the skull bursts or bleeds into and around the brain.
  • the injury to the brain caused by a stroke can lead to long lasting and widespread problems which can include reduced cognitive function leading to disruption in communication, spatial awareness, memory, concentration and executive functioning. Movement problems may also occur causing weakness, paralysis, and fatigue. Other symptoms which may occur after a stroke include loss of bladder or bowel control, visual problems, problems swallowing and seizures.
  • CBD Cannabidiol
  • CBD cannabinoids
  • Some cannabinoids including CBD have been found to have a neuroprotective effect and may be useful in the prevention of stroke 1 . However, until now there has been no evidence to show that CBD might be useful in the treatment of seizures associated with stroke or brain haemorrhage.
  • Applicant’s previous applications such as GB 2539472, GB 2531093 and GB 2531278 disclose the effectiveness of highly purified CBD in the treatment of various epileptic syndromes. However, none provide any data of patients with stroke or brain haemorrhage nor is there any mention of these conditions.
  • CBD cannabidiol
  • the seizures associated with stroke or brain haemorrhage are tonic, tonic-clonic, atonic, myoclonic, absence, focal seizures without impairment, focal seizures with impairment and focal seizures with secondary generalisation.
  • the CBD preparation comprises greater than 95% (w/w) CBD and not more than 0.15% (w/w) tetrahydrocannabinol (THC).
  • the CBD preparation comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) other cannabinoids, wherein the less than or equal to 2% (w/w) other cannabinoids comprise the cannabinoids tetrahydrocannabinol (THC); cannabidiol- C1 (CBD-C1); cannabidivarin (CBDV); and cannabidiol-C4 (CBD-C4), and wherein the THC is present as a mixture of trans-THC and cis-THC.
  • THC cannabinoids tetrahydrocannabinol
  • CBD-C1 cannabidiol- C1
  • CBDDV cannabidivarin
  • CBD-C4 cannabidiol-C4
  • the CBD preparation is used in combination with one or more concomitant anti-epileptic drugs (AED).
  • AED concomitant anti-epileptic drugs
  • the one or more AED is selected from the group consisting of: valproic acid, diazepam, topiramate, lacosamide, lamotrigine, zonisamide, clobazam, phenytoin, rufinamide, levetiracetam, and gabapentin.
  • the CBD is present is isolated from cannabis plant material.
  • the CBD is present as a synthetic preparation.
  • the dose of CBD is greater than 5 mg/kg/day. More preferably the dose of CBD is 20 mg/kg/day. More preferably the dose of CBD is 25 mg/kg/day. More preferably the dose of CBD is 50 mg/kg/day.
  • a method of treating seizures associated with stroke or brain haemorrhage comprising administering a cannabidiol (CBD) preparation to the subject in need thereof.
  • CBD cannabidiol
  • cannabinoids Over 100 different cannabinoids have been identified, see for example, Handbook of Cannabis, Roger Pertwee, Chapter 1, pages 3 to 15. These cannabinoids can be split into different groups as follows: Phytocannabinoids; Endocannabinoids and Synthetic cannabinoids (which may be novel cannabinoids or synthetically produced phytocannabinoids or endocannabinoids).
  • phytocannabinoids are cannabinoids that originate from nature and can be found in the cannabis plant.
  • the phytocannabinoids can be isolated from plants to produce a highly purified extract or can be reproduced synthetically.
  • “Highly purified cannabinoids” are defined as cannabinoids that have been extracted from the cannabis plant and purified to the extent that other cannabinoids and non-cannabinoid components that are co-extracted with the cannabinoids have been removed, such that the highly purified cannabinoid is greater than or equal to 95% (w/w) pure.
  • Synthetic cannabinoids are compounds that have a cannabinoid or cannabinoid-like structure and are manufactured using chemical means rather than by the plant.
  • Phytocannabinoids can be obtained as either the neutral (decarboxylated form) or the carboxylic acid form depending on the method used to extract the cannabinoids. For example, it is known that heating the carboxylic acid form will cause most of the carboxylic acid form to decarboxylate into the neutral form.
  • Treatment-resistant epilepsy (TRE) or “intractable epilepsy” is defined as per the I LAE guidance of 2009 as epilepsy that is not adequately controlled by trials of one or more AED.
  • Tonic seizures can be generalised onset, affecting both sides of the brain, or they can be focal onset, starting in just one side of the brain. If a tonic seizure starts in both sides of the brain, all muscles tighten and the subject’s body goes stiff. If standing, they may fall to the floor, their neck may extend, eyes open wide and roll upwards, whilst their arms may raise upwards and legs stretch or contract. If a tonic seizure starts in one side of the brain muscles tighten in just one area of the body. Tonic seizures usually last less than one minute.
  • Tonic-clonic seizures consist of two phases: the tonic phase and the clonic phase. In the tonic phase the body becomes entire rigid, and in the clonic phase there is uncontrolled jerking. Tonic-clonic seizures may or may not be preceded by an aura, and are often followed by headache, confusion, and sleep. They may last mere seconds or continue for several minutes. These seizures are also known as a grand mal seizure. [0042] “Atonic seizures” occur when a person suddenly loses muscle tone so their head or body may go limp. They are also known as drop attacks. In some children, only their head drops suddenly. They can begin in one area or side of the brain (focal onset) or both sides of the brain (generalized onset).
  • Myoclonic seizures are characterised by a ‘muscle jerk’. Myoclonic seizures are brief but can happen in clusters (many happening close together in time) and often happen shortly after waking. In myoclonic seizures the person is conscious, but they are classified as generalised seizures.
  • “Absence seizures” also may be called “petit mal” seizures. These types of seizure cause a loss of awareness for a short time. They mainly affect children although can happen at any age. During an absence seizure, a person may: stare blankly into space; look like they're "daydreaming"; flutter their eyes; make slight jerking movements of their body or limbs. The seizures usually only last up to 15 seconds and may occur several times a day.
  • “Focal Seizures” are defined as seizures which originate within networks limited to only one hemisphere. What happens during the seizure depends on where in the brain the seizure happens and what that part of the brain normally does.
  • “Focal seizures without impairment” are seizures which originate within networks limited to only one hemisphere where the awareness or responsiveness of the subject is not impaired.
  • “Focal seizure with impairment” usually start in a small area of the temporal lobe or frontal lobe of the brain and involve other areas of the brain within the same hemisphere that affect alertness and awareness. Most subjects experience automatisms during a focal seizure with impaired consciousness.
  • “Focal seizure with secondary generalisation” start in a limited area on one side of the brain and spread to involve both sides. This is different from a generalized onset seizure, which starts on both sides of the brain.
  • the drug substance used is a liquid carbon dioxide extract of high-CBD containing chemotypes of Cannabis sativa L. which had been further purified by a solvent crystallization method to yield CBD.
  • the crystallisation process specifically removes other cannabinoids and plant components to yield greater than or equal to 95% CBD.
  • CBD is highly purified because it is produced from a cannabis plant rather than synthetically there is a small number of other cannabinoids which are co-produced and co-extracted with the CBD. Details of these cannabinoids and the quantities in which they are present in the medication are as described in Table A below.
  • the drug substance used in the trials is a liquid carbon dioxide extract of high-CBD containing chemotypes of Cannabis sativa L. which had been further purified by a solvent crystallization method to yield CBD.
  • the crystallisation process specifically removes other cannabinoids and plant components to yield greater than 95% CBD w/w, typically greater than 98% w/w.
  • Cannabis sativa L. plants are grown, harvested, and processed to produce a botanical extract (intermediate) and then purified by crystallization to yield the CBD (botanically derived purified CBD).
  • the plant starting material is referred to as Botanical Raw Material (BRM); the botanical extract is the intermediate; and the active pharmaceutical ingredient (API) is CBD, the drug substance.
  • BRM Botanical Raw Material
  • API active pharmaceutical ingredient
  • Table B Specification of an exemplary botanically derived purified CBD preparation
  • the purity of the botanically derived purified CBD preparation was greater than or equal to 98%.
  • the botanically derived purified CBD includes THC and other cannabinoids, e.g., CBDA, CBDV, CBD-C1, and CBD-C4.
  • the CBD preparation comprises not more than 0.15% THC based on total amount of cannabinoid in the preparation. In some embodiments, the CBD preparation comprises about 0.01% to about 0.1% THC based on total amount of cannabinoid in the preparation. In some embodiments, the CBD preparation comprises about 0.02% to about 0.05% THC based on total amount of cannabinoid in the preparation.
  • the CBD preparation comprises about 0.2% to about 1.0% CBDV based on total amount of cannabinoid in the preparation. In some embodiments, the CBD preparation comprises about 0.2% to about 0.8% CBDV based on total amount of cannabinoid in the preparation. [0059] In some embodiments, the CBD preparation comprises about 0.3% to about 0.5%
  • CBD-C4 based on total amount of cannabinoid in the preparation.
  • the CBD preparation comprises about 0.3% to about 0.4% CBD-C4 based on total amount of cannabinoid in the preparation.
  • the CBD preparation comprises about 0.1% to about 0.15% CBD-C1 based on total amount of cannabinoid in the preparation.
  • Distinct chemotypes of the Cannabis sativa L. plant have been produced to maximize the output of the specific chemical constituents, the cannabinoids. Certain chemovars produce predominantly CBD. Only the (-)-trans isomer of CBD is believed to occur naturally. During purification, the stereochemistry of CBD is not affected.
  • High CBD chemovars were grown, harvested, dried, baled and stored in a dry room until required.
  • the botanical raw material (BRM) was finely chopped using an Apex mill fitted with a 1 mm screen. The milled BRM was stored in a freezer prior to extraction.
  • the BDS produced using the methodology above was dispersed in C5-C12 straight chain or branched alkane.
  • the mixture was manually agitated to break up any lumps and the sealed container then placed in a freezer for approximately 48 hours.
  • the crystals were isolated via vacuum filtration, washed with aliquots of cold C5-C12 straight chain or branched alkane, and dried under a vacuum of ⁇ 10mb at a temperature of 60°C until dry.
  • the botanically derived purified CBD preparation was stored in a freezer at -20°C in a pharmaceutical grade stainless steel container, with FDA food grade approved silicone seal and clamps.
  • the botanically derived purified CBD used in the clinical trial described in the invention comprises greater than or equal to 98% (w/w) CBD and less than or equal to 2% (w/w) of other cannabinoids.
  • the other cannabinoids present are THC at a concentration of less than or equal to 0.1% (w/w); CBD-C1 at a concentration of less than or equal to 0.15% (w/w); CBDV at a concentration of less than or equal to 0.8% (w/w); and CBD-C4 at a concentration of less than or equal to 0.4% (w/w).
  • the botanically derived purified CBD used additionally comprises a mixture of both trans-THC and cis-THC. It was found that the ratio of the trans-THC to cis-THC is altered and can be controlled by the processing and purification process, ranging from 3.3:1 (trans-THC:cis- THC) in its unrefined decarboxylated state to 0.8:1 (trans-THC:cis-THC) when highly purified. [0070] Furthermore, the cis-THC found in botanically derived purified CBD is present as a mixture of both the (+)-cis-THC and the (-)-cis-THC isoforms.
  • CBD preparation could be produced synthetically by producing a composition with duplicate components.
  • Example 1 describes the use of a botanically derived purified CBD in an open label, expanded-access program to investigate the clinical efficacy and safety of purified pharmaceutical cannabidiol formulation (CBD) in the treatment of patients diagnosed with stroke or brain haemorrhage.
  • CBD cannabidiol formulation
  • EXAMPLE 1 CLINICAL EFFICACY AND SAFETY OF PURIFIED PHARMACEUTICAL CANNABIDIOL (CBD) IN THE TREATMENT OF PATIENTS DIAGNOSED WITH STROKE OR BRAIN HAEMORRHAGE. Study design
  • Subjects were required to be on one or more AEDs at stable doses for a minimum of two weeks prior to baseline and to have stable vagus nerve stimulation (VNS) settings and ketogenic diet ratios for a minimum of four weeks prior to baseline.
  • VNS vagus nerve stimulation
  • a maximum dose of 50 mg/kg/day could be utilised for patients who were tolerating the medication but had not achieved seizure control; these patients had further weekly titration by 5mg/kg/day.
  • Seizure frequency, intensity, and duration were recorded by caregivers in a diary during a baseline period of at least 28 days. Changes in seizure frequency relative to baseline were calculated after at least 2 weeks and at defined timepoints of treatment.
  • Patients may be defined as responders if they had more than 50% reduction in seizure frequency compared to baseline.
  • the percent change in seizure frequency was calculated as follows:
  • % change (weekly seizure frequency time interval) - (weekly seizure frequency Baseline) seizure frequency (weekly seizure frequency Baseline)
  • the percent change of seizure frequency may be calculated for any time interval where seizure number has been recorded.
  • the percent change of seizure frequency for the end of the treatment period was calculated as follows:
  • % reduction ((weekly seizure frequency Baseline) - (weekly seizure frequency End)) x100 seizure frequency (weekly seizure frequency Baseline)
  • Table 1 Patient demographics, seizure type and concomitant medication
  • VPA valproic acid
  • DPM diazepam
  • TOP topiramate
  • LAC lacosamide
  • LTG lamotrigine
  • ZON zonisamide
  • CLB clobazam
  • PHY phenytoin
  • RFN rufinamide
  • LEV levetiracetam
  • GBP gabapentin Study medication and concomitant medications
  • Tables 2A-2I illustrate the seizure frequency for each patient as well as the dose of CBD given.
  • Table 2A Seizure frequency data for Patient 1
  • Patient 5 was treated for 108 weeks and experienced a 35% reduction in absence seizures and a 50% reduction in focal seizures with impairment over the treatment period.
  • Table 2F Seizure frequency data for Patient 6 [0090] Patient 6 was treated for 72 weeks and experienced a 100% reduction in tonic seizures and a 100% reduction in absence seizures over the treatment period.
  • Patient 7 was treated for 144 weeks and experienced a 9.5% reduction in focal seizures with secondary generalisation over the treatment period.
  • Table 2H Seizure frequency data for Patient 8 [0092] Patient 8 was treated for 4 weeks and experienced a 100% reduction in tonic seizures, tonic-clonic seizures and absence seizures over the treatment period.
  • CBD was effective in reducing the frequency of the following seizure types: tonic, tonic-clonic, atonic, absence, focal seizures with impairment, focal seizures without impairment and focal seizures with secondary generalisation. [0096] Significantly, two patients became seizure free of tonic seizures after 72 weeks and
  • CBD was able to significantly reduce the number of seizures associated with stroke or brain haemorrhage.
  • the treatment is of significant benefit in this difficult to treat epilepsy syndrome given the high responder rate experienced in many of the patients.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Botany (AREA)
  • Neurology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Mycology (AREA)
  • Pain & Pain Management (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne l'utilisation de cannabidiol (CBD) pour le traitement de crises associées à un accident vasculaire cérébral ou à une hémorragie cérébrale. Dans un autre mode de réalisation, les types de crises comprennent les crises toniques, tonicocloniques, atoniques, myocloniques, d'absence, les crises focales sans altération de la conscience, les crises focales avec altération de la conscience et les crises focales avec une généralisation secondaire. De préférence, la dose de CBD est comprise entre 5 mg/kg/jour et 50 mg/kg/jour.
PCT/EP2021/069898 2020-07-20 2021-07-15 Utilisation de cannabidiol dans le traitement de crises associées à un accident vasculaire cérébral ou à une hémorragie cérébrale WO2022017957A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB2011149.8 2020-07-20
GB2011149.8A GB2597302A (en) 2020-07-20 2020-07-20 Use of cannabidiol in the treatment of seizures associated with stroke or brain haemorrhage

Publications (1)

Publication Number Publication Date
WO2022017957A1 true WO2022017957A1 (fr) 2022-01-27

Family

ID=72339042

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2021/069898 WO2022017957A1 (fr) 2020-07-20 2021-07-15 Utilisation de cannabidiol dans le traitement de crises associées à un accident vasculaire cérébral ou à une hémorragie cérébrale

Country Status (2)

Country Link
GB (1) GB2597302A (fr)
WO (1) WO2022017957A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999053917A1 (fr) * 1998-04-21 1999-10-28 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Cannabinoides comme antioxydants et neuroprotecteurs
GB2531093A (en) 2014-06-17 2016-04-13 Gw Pharma Ltd Use of cannabidiol in the reduction of convulsive seizure frequency in treatment-resistant epilepsy
GB2531282A (en) * 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabinoids in the treatment of epilepsy
GB2531278A (en) 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabidiol in the treatment of intractable epilepsy
GB2539472A (en) 2015-06-17 2016-12-21 Gw Res Ltd Use of cannabinoids in the treatment of epilepsy
WO2019207319A1 (fr) * 2018-04-27 2019-10-31 GW Research Limited Préparations de cannabidiol et leurs utilisations

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2531280A (en) * 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabidiol in the treatment of intractable epilepsy

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999053917A1 (fr) * 1998-04-21 1999-10-28 The Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services Cannabinoides comme antioxydants et neuroprotecteurs
GB2531093A (en) 2014-06-17 2016-04-13 Gw Pharma Ltd Use of cannabidiol in the reduction of convulsive seizure frequency in treatment-resistant epilepsy
GB2531282A (en) * 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabinoids in the treatment of epilepsy
GB2531278A (en) 2014-10-14 2016-04-20 Gw Pharma Ltd Use of cannabidiol in the treatment of intractable epilepsy
GB2539472A (en) 2015-06-17 2016-12-21 Gw Res Ltd Use of cannabinoids in the treatment of epilepsy
WO2019207319A1 (fr) * 2018-04-27 2019-10-31 GW Research Limited Préparations de cannabidiol et leurs utilisations

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
CARABALLO ROBERTO ET AL: "Effectiveness of cannabidiol in a prospective cohort of children with drug-resistant epileptic encephalopathy in Argentina", SEIZURE, BAILLIERE TINDALL, LONDON, GB, vol. 80, 6 June 2020 (2020-06-06), pages 75 - 80, XP086246226, ISSN: 1059-1311, [retrieved on 20200606], DOI: 10.1016/J.SEIZURE.2020.06.005 *
EMILY STOCKINGS ET AL: "Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence", JOURNAL OF NEUROLOGY NEUROSURGERY & PSYCHIATRY., vol. 89, no. 7, 6 March 2018 (2018-03-06), GB, pages 741 - 753, XP055657257, ISSN: 0022-3050, DOI: 10.1136/jnnp-2017-317168 *
GRAYSON LESLIE ET AL: "An interaction between warfarin and cannabidiol, a case report", EPILEPSY & BEHAVIOR CASE REPORTS, vol. 9, 1 January 2018 (2018-01-01), NL, pages 10 - 11, XP055848771, ISSN: 2213-3232, DOI: 10.1016/j.ebcr.2017.10.001 *
HAYAKAWA ET AL.: "Therapeutic Potential of Non-Psychotropic Cannabidiol in Ischemic Stroke", PHARMACEUTICALS, 2010
LAUX LINDA C ET AL: "Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results", EPILEPSY RESEARCH, vol. 154, 25 March 2019 (2019-03-25), pages 13 - 20, XP085711365, ISSN: 0920-1211, DOI: 10.1016/J.EPLEPSYRES.2019.03.015 *
MARÍA RODRÍGUEZ-MUÑOZ ET AL: "Cannabidiol enhances morphine antinociception, diminishes NMDA-mediated seizures and reduces stroke damage via the sigma 1 receptor", MOLECULAR BRAIN, vol. 11, no. 1, 17 September 2018 (2018-09-17), XP055660650, DOI: 10.1186/s13041-018-0395-2 *
ROGER PERTWEE, HANDBOOK OF CANNABIS, pages 3 - 15
SERENA SILVESTRO ET AL: "Use of Cannabidiol in the Treatment of Epilepsy: Efficacy and Security in Clinical Trials", MOLECULES, vol. 24, no. 8, 12 April 2019 (2019-04-12), pages 1459, XP055715278, DOI: 10.3390/molecules24081459 *

Also Published As

Publication number Publication date
GB202011149D0 (en) 2020-09-02
GB2597302A (en) 2022-01-26

Similar Documents

Publication Publication Date Title
EP4182024A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des mutations dans le gène syngap1
WO2022017957A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à un accident vasculaire cérébral ou à une hémorragie cérébrale
WO2022017930A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées au syndrome de jeavon
EP4181888A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017920A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017944A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à une dégénérescence cérébrale bilatérale
WO2022017915A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à des lésions cérébrales
EP4181890A1 (fr) Utilisation du cannabidiol dans le traitement de crises associées au syndrome de rett
EP4181891A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à un traumatisme cérébral
WO2022017958A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées au syndrome du bébé secoué
WO2022017954A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017917A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau
WO2022017929A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à la lissencéphalie
WO2022017919A1 (fr) Cannabidiol destiné à être utilisé dans le traitement de crises associées à une hydrocéphalie
WO2022017909A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes d'épilepsies rares associées à des anomalies structurales du cerveau
WO2022123236A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques chez des patients prenant du brivaracétam
GB2597278A (en) Use of cannabidiol in the treatment of seizures associated with rare epilepsy syndromes related to structural abnormalities of the brain
EP4181893A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
EP4181902A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017936A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes d'épilepsies rares liés à des anomalies structurales du cerveau
WO2022017963A1 (fr) Utilisation de cannabidiol dans le traitement de crises d'épilepsie associées à une encéphalite
WO2022017947A1 (fr) Utilisation du cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017946A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies génétiques
WO2022017956A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées au virus de l'herpès simplex
WO2022017955A1 (fr) Utilisation de cannabidiol dans le traitement de crises associées à des syndromes épileptiques rares liés à des anomalies structurales du cerveau

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21751755

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21751755

Country of ref document: EP

Kind code of ref document: A1