WO2024042526A1 - Compositions de cannabis enrichies en cannflavine pour un effet thérapeutique cohérent sur diverses affections - Google Patents

Compositions de cannabis enrichies en cannflavine pour un effet thérapeutique cohérent sur diverses affections Download PDF

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Publication number
WO2024042526A1
WO2024042526A1 PCT/IL2023/050899 IL2023050899W WO2024042526A1 WO 2024042526 A1 WO2024042526 A1 WO 2024042526A1 IL 2023050899 W IL2023050899 W IL 2023050899W WO 2024042526 A1 WO2024042526 A1 WO 2024042526A1
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Prior art keywords
cannflavin
cannabis
composition
daily dose
per daily
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PCT/IL2023/050899
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English (en)
Inventor
Sarah KORNBLAU
Genia LEVINTON
Shany HERSKOVITS
Anat RAPOPORT
Leehee BARAK
Eran Goldberg
Shifra JAMMER
Dadi Segal
Or SEGAL
Lior Zelikovich
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Panaxia Pharmaceutical Industries Ltd.
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Publication of WO2024042526A1 publication Critical patent/WO2024042526A1/fr

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    • 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
    • A61P25/20—Hypnotics; Sedatives
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A61K31/658—Medicinal preparations containing organic active ingredients o-phenolic cannabinoids, e.g. cannabidiol, cannabigerolic acid, cannabichromene or tetrahydrocannabinol
    • 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)
    • A61K36/348—Cannabaceae
    • A61K36/3482—Cannabis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • 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
    • A61P25/22—Anxiolytics

Definitions

  • the present disclosure generally relates to cannabis compositions having a particular content of cannflavin and use of the cannabis composition for the treatment of various conditions.
  • Cannabis has become more and more widespread in medical treatments and has shown to have various benefits.
  • CBD cannabidiol
  • THC tetrahydrocannabinol
  • terpenoids and flavonoids present in various amounts and ratios, are also found in cannabis, for example, cannflavin.
  • insomnia which is the most common, as well as from circadian rhythm sleep-wake phase disorders, sleep apnea, restless legs syndrome, and many more.
  • insomnia is co-morbid with other medical, neurological and/or psychiatric conditions, for example, Post-Traumatic Stress Disorder (PTSD).
  • PTSD Post-Traumatic Stress Disorder
  • sleep difficulties and pain may be associated with fibromyalgia (FM) patients, and anxiety and pain may simultaneously exist with tumor progression in cancer patients.
  • FM fibromyalgia
  • insomnia can be managed with adequate medications, and other interventions including behavioral and psychotherapeutic treatments.
  • Drug-based interventions used in the treatment of these conditions and symptoms may include any of melatonin and agonists thereof, benzodiazepines, antidepressants including selective serotonin reuptake inhibitors (SSRI), dopamine-agonists, gabapentin, and narcotics, including opioids and others; however, these have adverse side effects including cognitive impairment, daytime sedation, dizziness, weight gain, metabolic syndromes, and have the potential for addiction.
  • SSRI selective serotonin reuptake inhibitors
  • opioids and others including opioids and others; however, these have adverse side effects including cognitive impairment, daytime sedation, dizziness, weight gain, metabolic syndromes, and have the potential for addiction.
  • the present disclosure provides cannabis compositions comprising cannabis molecules, namely cannflavin, that surprisingly was found to be positively correlated with treatment efficacy of various conditions and/or symptoms.
  • a cannabis composition comprising a predetermined minimal amount/concentration of cannflavin per daily dose is efficacious for use in the treatment of various conditions and/or symptoms, including sleep difficulties, pain, headaches, abdominal pain, and anxiety.
  • the disclosure provides cannabis compositions, standardized cannabis extract and methods of treatment including the same.
  • the disclosure provides methods of evaluating such compositions for having a particular content that makes them suitable for efficacious treatment, thereby the method allows classifying and labeling these cannabis compositions for use in the treatment of sleep difficulties, pain, headaches, abdominal pain, and/or anxiety.
  • compositions and methods including at least a minimal ratio of cannflavin and THC concentrations that found to be positively correlated with efficacious treatment; and yet in additional embodiments, disclosed is a surprising combination of cannflavin and CBN at their disclosed predetermined minimal amount/concentration that was also found to correlate to treatment efficacy.
  • a cannabis composition of the invention may fulfil one or more characteristics required for it to be suitable for efficacious treatment, including (i) at least a predetermined minimal amount/concentration of cannflavin per daily dose; (ii) cannflavin to THC and/or cannflavin to CBD concentrations at least at the minimal characteristic ratio required for efficacious treatment; (iii) enriched amount of cannflavin of at least twice the predetermined minimal amount/concentration; and (iv) a combination of cannflavin at least at its predetermined minimal amount and at least a minimal amount of CBN.
  • a cannabis composition comprising a predetermined minimal amount/concentration of at least 40ug cannflavin, per daily dose for use in a treatment of a condition and/or symptom in a subject in need thereof, said condition and/or symptom comprises sleep difficulties.
  • Eash possibility is a separate embodiment.
  • a cannabis composition comprising a predetermined minimal amount/concentration of at least 40ug cannflavin, per daily dose for use in a treatment of one more condition and/or symptom in a subject in need thereof, said one more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • Eash possibility is a separate embodiment.
  • the predetermined minimal amount is at least 60 ug cannflavin, per daily dose.
  • the composition comprises cannflavin and THC at concentrations characterized by a cannflavin to THC ratios of at least about 0.070%.
  • the composition comprises cannflavin and CBD at concentrations characterized by a cannflavin to CBD ratios of at least about 27%.
  • the composition further comprises a CBN at an amount of at least 825ug per daily dose.
  • the composition comprises raw cannabis.
  • the cannflavin in the composition comprises extracted, isolated, purified, and/or synthetic cannflavin, or any combination thereof. Eash possibility is a separate embodiment.
  • the composition is selected from a plurality of potential cannabis compositions based on an analysis of the content of cannflavin in the plurality of potential cannabis compositions.
  • cannflavin is added to the composition when the cannflavin content is below the predetermined minimal amount/concentration.
  • At least a portion of the cannflavin in the composition comprises extracted, isolated and/or synthetic cannflavin, or any combination thereof. Each possibility is a separate embodiment.
  • the administering comprises administering by route of smoking, inhalation, vaporization, oral administration, buccal administration, nasal administration, topical administration, transdermal administration parenteral administration, or any combination thereof.
  • route of smoking inhalation, vaporization, oral administration, buccal administration, nasal administration, topical administration, transdermal administration parenteral administration, or any combination thereof.
  • At least one of the conditions and/or symptoms is characterized by a high level of perceived severity, and wherein the high level of perceived severity comprises self-reported ranking of 4 or 5 on a scale of 1-5.
  • the high level of perceived severity comprises self-reported ranking of 4 or 5 on a scale of 1-5.
  • At least one condition and/or symptom is associated with at least one additional medical condition.
  • Each possibility is a separate embodiment.
  • At least one condition and/or symptom is associated with at least one additional medical condition; and wherein the at least one additional medical condition includes Post-Traumatic Stress Disorder (PTSD), fibromyalgia (FM), Inflammatory Bowel Disease (IBD), cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • Post-Traumatic Stress Disorder PTSD
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • cancer pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • condition and/or symptom comprises sleeping difficulties.
  • Each possibility is a separate embodiment.
  • the sleep difficulties comprise one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep Tight sleep’, fragmented/impaired sleep, and insufficient sleep, or any combination thereof.
  • the sleep difficulties comprise one or more sleep disorders comprising insomnia, and/or circadian rhythms sleep-wake phase disorder (SWPD).
  • SWPD sleep-wake phase disorder
  • the sleep disorder comprises insomnia.
  • the sleep difficulties are associated with at least one additional medical condition; and wherein the at least one additional medical condition includes Post-Traumatic Stress Disorder PTSD, fibromyalgia (FM) and/or cancer, or any combination thereof.
  • Post-Traumatic Stress Disorder PTSD fibromyalgia
  • FM fibromyalgia
  • cancer or any combination thereof.
  • the one or more condition and/or symptom comprises pain.
  • Each possibility is a separate embodiment.
  • the pain comprises one or more of orthopedic pain, muscle pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof.
  • orthopedic pain muscle pain
  • spinal disc herniation pain neuropathic pain
  • widespread pain abdominal pain
  • headaches or any combination thereof.
  • the pain is associated with at least one additional medical condition; and wherein the at least one additional medical condition includes fibromyalgia (FM), Inflammatory Bowel Disease (IBD) and/or cancer, or any combination thereof.
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • the one or more condition and/or symptom comprises abdominal pain.
  • abdominal pain each possibility is a separate embodiment.
  • the abdominal pain is associated with at least one additional medical condition; and wherein the at least one additional medical condition includes fibromyalgia (FM) and/or Inflammatory Bowel Disease (IBD).
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • the one or more condition and/or symptom comprises headaches.
  • Each possibility is a separate embodiment.
  • the composition further comprises CBN at an amount of at least 825ug per daily dose.
  • the one or more condition and/or symptom comprises anxiety.
  • anxiety is associated with at least one additional medical condition; and wherein the at least one additional medical condition comprise fibromyalgia (FM) and/or cancer.
  • FM fibromyalgia
  • the composition comprises a standardized extract.
  • the composition comprises a standardized extract comprising at least about 2.6% (w/w) THC, at least about 2.6% (w/w) CBD, at least about 0.005% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • a standardized extract comprising at least about 2.6% (w/w) THC, at least about 2.6% (w/w) CBD, at least about 0.005% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • the composition comprises a standardized extract comprising at least about 5.2% (w/w) THC, at least about 5.2% (w/w) CBD, at least about 0.01% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • a standardized extract comprising at least about 5.2% (w/w) THC, at least about 5.2% (w/w) CBD, at least about 0.01% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • the composition comprises cannabis extracts enriched with cannflavin.
  • the cannabis extracts enriched with cannflavin comprises at least about 2 times the predetermined minimal amount/concentration of cannflavin.
  • the cannabis extract enriched with cannflavin comprises at least about 200 times the predetermined minimal amount/concentration of cannflavin.
  • the composition comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug, per daily dose.
  • the composition comprises cannflavin at maximal concentration of less than 5.0000%.
  • At least a portion of the cannflavin in the composition comprises extracted, isolated, purified, and/or synthetic cannflavin. Each possibility is a separate embodiment. In some embodiments, at least a portion of the cannflavin in the cannabis composition comprises isolated and/or synthetic cannflavin. Each possibility is a separate embodiment.
  • the cannflavin includes cannflavin A.
  • a method for classifying cannabis compositions as being suitable for the treatment of one or more condition and/or symptom comprising: receiving a potential cannabis composition; evaluating the content of cannflavin in the potential cannabis composition; classifying the composition as being suitable for the treatment of the one or more condition and/or symptom when the cannflavin content is at or above a predetermined minimal amount/concentration of 40ug, per daily dose; and wherein the one or more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof.
  • the predetermined minimal amount is at least 60ug, per daily dose.
  • the classification method further comprises labeling the potential composition as being suitable for the treatment of one or more of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof, when the cannflavin content is at or above the predetermined minimal amount/concentration.
  • the potential composition is labeling the potential composition as being suitable for the treatment of one or more of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof, when the cannflavin content is at or above the predetermined minimal amount/concentration.
  • labeling the potential composition as being suitable for the treatment of sleep difficulties comprises labeling the composition as being suitable for the treatment of sleep disorder including insomnia and/or circadian rhythms sleep-wake phase disorder (SWPD).
  • sleep disorder including insomnia and/or circadian rhythms sleep-wake phase disorder (SWPD).
  • SWPD sleep-wake phase disorder
  • the cannflavin includes cannflavin A.
  • a standardized cannabis extract comprising extracts from a natural source and isolated and/or synthetic cannflavin; wherein the extract comprises cannflavin at a predetermined minimal amount/concentration of at least 40ug per daily dose.
  • the predetermined minimal amount is at least 60ug, per daily dose.
  • the standardized extract comprises cannflavin and THC at concentrations characterized by a cannflavin to THC ratio of at least about at least about 0.070%.
  • the standardized extract comprises cannflavin and CBD at concentrations characterized by a cannflavin to CBD ratios of at least about 27%.
  • the standardized extract further comprises CBN at an amount of at least 825ug per daily dose.
  • the standardized extract comprises at least about 2.6% (w/w) THC, at least about 2.6% (w/w) CBD, at least about 0.005% (w/w) cannflavin and optionally about 0.5% (w/w) Vitamin E.
  • THC at least about 2.6% (w/w) THC
  • CBD at least about 2.6% (w/w) CBD
  • 0.005% w/w
  • cannflavin at least about 0.5% (w/w) Vitamin E.
  • the standardized extract comprises at least about 5.2% (w/w) THC, at least about 5.2% (w/w) CBD, at least about 0.01% (w/w) cannflavin and optionally about 0.5% (w/w) Vitamin E.
  • THC at least about 5.2%
  • CBD at least about 5.2%
  • cannflavin at least about 0.01%
  • cannflavin at least about 0.5%
  • Vitamin E optionally about 0.5%
  • the standardized extract is enriched with cannflavin; and wherein the cannabis extract enriched with cannflavin comprises at least about 2 times the predetermined minimal amount/concentration of cannflavin.
  • the standardized extract comprises cannflavin at an amount between the predetermined minimal amount and a maximum amount of about 500,000ug, per daily dose.
  • the composition comprises cannflavin at maximal concentration of less than 5.0000%.
  • the cannflavin includes cannflavin A.
  • a method for treating one or more condition and/or symptom in a subject in need thereof comprising: administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin, and wherein the one more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin
  • the one more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • the predetermined minimal amount is at least 60 ug cannflavin, per daily dose.
  • the administering comprises administering by route of smoking, inhalation, vaporization, oral administration, buccal administration, nasal administration, topical administration, transdermal administration parenteral administration, or any combination thereof.
  • At least one condition and/or symptom is characterized by a high level of perceived severity, and wherein the high level of perceived severity comprises self- reported ranking of 4 or 5 on a scale of 1-5.
  • the high level of perceived severity comprises self- reported ranking of 4 or 5 on a scale of 1-5.
  • At least one condition and/or symptom is associated with at least one additional medical condition.
  • Each possibility is a separate embodiment.
  • the one or more condition and/or symptom comprises sleep difficulties.
  • sleep difficulties Each possibility is a separate embodiment.
  • the sleep difficulties comprise one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep ‘light sleep’, fragmented/impaired sleep, and insufficient sleep, or any combination thereof.
  • the sleep difficulties comprise one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep ‘light sleep’, fragmented/impaired sleep, and insufficient sleep, or any combination thereof.
  • the sleep difficulties comprise one or more sleep disorders.
  • the one or more sleep disorders comprise insomnia, and/or circadian rhythms sleep-wake phase disorder (SWPD).
  • SWPD sleep-wake phase disorder
  • the one or more condition and/or symptom comprises pain.
  • Each possibility is a separate embodiment.
  • the pain comprises one or more of orthopedic pain, muscle pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof.
  • the one or more condition and/or symptom comprises abdominal pain.
  • the one or more condition and/or symptom comprises headaches.
  • Each possibility is a separate embodiment.
  • the one or more condition and/or symptom comprises anxiety.
  • Each possibility is a separate embodiment.
  • the present disclosure provides cannabis compositions, and methods of evaluating such compositions for having a particular content that makes them suitable for use in the treatment of sleep disorders, as well as methods for treating sleep disorders using the composition.
  • cannabis compositions including a certain amount of cannflavin, provide a consistent beneficial outcome with regard to treating/reducing/attenuating/preventing sleep problems, for example, in subjects suffering from Post-Traumatic Stress Disorder (PTSD).
  • PTSD Post-Traumatic Stress Disorder
  • the inventors further found the positive effect was further enhanced in cannabis compositions including a predetermined minimal amount/concentration of cannflavin.
  • the herein disclosed finding allows avoiding compositions that do not provide a consistent beneficial outcome thereby attenuating/preventing the possible undesired side effect of having troubles/difficulties sleeping due to cannabis consumption.
  • a method for treating sleep disorder of a subject in need thereof comprising: administering a therapeutically effective amount of a suitable cannabis composition to the subject, the suitable cannabis composition characterized by comprising predetermined minimal amount/concentration of cannflavin, thereby improving the sleep disorder.
  • the sleep disorder comprises at least one sleep problem selected from the group consisting of subject’s complaints of trouble sleeping, difficulty in initiating sleep (i.e., falling asleep), difficulty in maintaining sleep (i.e., staying asleep/continuous sleep), experiencing impaired sleep, fragmented sleep, poor sleep, having low-quality sleep (i.e., not a good sleep), insufficient sleep, difficulty waking up, experiencing excessive sleepiness, having movements of legs or limbs during sleep, abnormal muscle tonus (i.e., contraction) during sleep, disordered/abnormal breathing/respiration during sleep, and/or snoring, or any combination thereof.
  • subject a different embodiment.
  • the sleep disorder further comprises alterations in sleep phases.
  • the sleep disorder is associated with at least one of dysfunctions in the endocrine body system, metabolic body system, nervous body system, higher cortical function, neurological disorders, or any combination thereof.
  • dysfunctions in the endocrine body system metabolic body system, nervous body system, higher cortical function, neurological disorders, or any combination thereof.
  • the sleep disorder is primary or secondary.
  • the secondary sleep disorder is associated with at least one of medical, neurological, and/or psychiatric condition selected from Post-Traumatic Stress Disorder (PTSD), depression, anxiety, Neurodegenerative diseases (such as multiple system atrophy (MSA), Parkinson's disease (PD) and Lewy body disease (LBD) or Alzheimer's disease (AD)), Schizophrenia, and Bipolar disorder, or any combination thereof.
  • PTSD Post-Traumatic Stress Disorder
  • depression anxiety
  • Neurodegenerative diseases such as multiple system atrophy (MSA), Parkinson's disease (PD) and Lewy body disease (LBD) or Alzheimer's disease (AD)
  • MSA multiple system atrophy
  • PD Parkinson's disease
  • LBD Lewy body disease
  • AD Alzheimer's disease
  • Schizophrenia a separate embodiment.
  • the secondary sleep disorder is associated with Post- Traumatic Stress Disorder (PTSD).
  • PTSD Post- Traumatic Stress Disorder
  • the sleep disorder is selected from at least one of insomnia, parasomnias, circadian rhythms advanced sleep-wake phase disorder (ASWPD), circadian rhythms delayed sleep-wake phase disorder (DSWPD), sleep disordered breathing (SDB) sleep apnea (SA), obstructive sleep apnea (OSA), rapid-eye movement (REM) behavior disorder, non-rapid-eye movement parasomnia (NREM parasomnia), restless legs syndrome (RLS), periodic limb movement of sleep (PLMS), bruxism, nocturia, sleepwalking, snoring, and narcolepsy, or any combination thereof.
  • insomnia circadian rhythms advanced sleep-wake phase disorder
  • DSWPD circadian rhythms delayed sleep-wake phase disorder
  • SDB sleep disordered breathing
  • SA sleep apnea
  • OSA obstructive sleep apnea
  • REM rapid-eye movement
  • NREM parasomnia non-rapid
  • the sleep disorder is insomnia
  • improving the sleep disorder comprises improving at least one sleep problem, at least 2 sleep problems, at least 3 sleep problems, at least 4 sleep problems, at least 5 sleep problems, at least 6 sleep problems, at least 7 sleep problems, at least 8 sleep problems, at least 9 sleep problems, at least 10 sleep problems or more.
  • Each possibility is a separate embodiment.
  • improving the sleep disorder comprises improving at least one sleep parameter selected from severity, frequency, intensity, and duration, or any combination thereof. Each possibility is a separate embodiment.
  • improving the sleep disorder comprises improving at least one symptom selected from subject’s complaints of distress and daytime impairment, reduced performance/productivity in daytime tasks and activities, problems with attention and concentration, low energy, fatigue, sleepiness, mood disturbance/irritability, aggressiveness, and impulsiveness, adversely affected interpersonal relationships, or any combination thereof.
  • subject selected from subject’s complaints of distress and daytime impairment, reduced performance/productivity in daytime tasks and activities, problems with attention and concentration, low energy, fatigue, sleepiness, mood disturbance/irritability, aggressiveness, and impulsiveness, adversely affected interpersonal relationships, or any combination thereof.
  • the predetermined minimal amount is at least 13 ug, per daily dose. According to some embodiments, the predetermined minimal amount is at least 21 ug, per daily dose.
  • the suitable cannabis compositions comprise raw cannabis. According to some embodiments, the suitable cannabis compositions comprise cannabis extracts. According to some embodiments, the suitable cannabis compositions comprise synthetic cannabis. According to some embodiments, the suitable cannabis compositions comprise isolated cannabis.
  • the cannflavin comprises synthetic, extracted, isolated, and/or purified cannflavin.
  • the method further comprises selecting the suitable cannabis composition from a plurality of cannabis compositions, wherein the selecting comprises analyzing the content of cannflavin in the plurality of cannabis compositions. According to some embodiments, the method further comprises adding cannflavin to the composition if the cannflavin content is below the predetermined minimal amount/concentration.
  • the administering comprises smoking, inhalation, vaporization, oral administration, buccal administration, nasal administration, topical administration, transdermal administration parenteral administration, or any combination thereof.
  • a cannabis composition comprising a predetermined minimal amount/concentration of cannflavin.
  • the predetermined minimal amount is at least 13 ug, per daily dose. According to some embodiments, the predetermined minimal amount is at least 21 ug, per daily dose.
  • At least a portion of the cannflavin in the cannabis compositions comprise synthetic, extracted, isolated and/or purified cannflavin.
  • the cannabis composition is selected from a plurality of potential cannabis compositions based on an analysis of the content of cannflavin in the plurality of potential cannabis compositions.
  • the administering comprises smoking, inhalation, vaporization, oral administration, buccal administration, nasal administration, topical administration, transdermal administration parenteral administration or any combination thereof.
  • a method for classifying cannabis compositions as being suitable for the treatment of sleep disorders comprises: receiving a potential cannabis composition; evaluating the content of cannflavin in the potential cannabis composition; classifying the composition as being suitable for the treatment of sleep disorder when the cannflavin content is at or above a predetermined minimal amount/concentration.
  • the predetermined minimal amount is at least 13 ug, per daily dose.
  • the predetermined minimal amount is at least 21 ug, per daily dose.
  • the method further comprises labeling the potential composition as being suitable for the treatment of sleep disorder when the cannflavin content is at or above the predetermined minimal amount/concentration.
  • a method for treating sleep disorder of a subject in need thereof comprising: administering to the subject a therapeutically effective amount of a composition comprising a predetermined minimal amount/concentration of synthetic, extracted, isolated, and/or purified cannflavin.
  • a cannabis extract comprising a predetermined minimal amount/concentration of isolated cannflavin.
  • FIG. 1 shows a typical overlay of chromatograms of the specific HPLC method applied in this study (obtained at 235nm wavelength) presenting Cannflavin A standard (blue line), an inflorescence sample as-is (green line; ratio of 1:1 herbal substance: methanol) and the same inflorescence sample spiked with Cannflavin A standard (red line; ratio 1:2 herbal substance: cannflavin A.
  • FIGs. 2A-2B show line graphs presenting the UV spectra of cannflavin A across all samples obtained using HPLC (FIG. 2A) and the UV spectra obtained for cannflavin A standard (FIG. 2B).
  • FIG. 2C shows line graphs presenting the UV spectra of all 59 clusters (each cluster representing a cannabis molecule).
  • FIG. 4 shows a multiple linear regression model presenting ranked treatment efficacy of pain vs. ranked concentrations of total CBN and Cannflavin A across 13 strains.
  • the regression model is illustrated by the pink plane. Strains are identified on the plot by their two letters initials. The differences of the predicted efficacies of each strain from their actual values are illustrated by the vertical red lines connecting the strains dots to the regression plane.
  • FIG. 5 schematically illustrates the basic design principle of the clinical trial being performed to evaluate the effect of standardized cannabis extracts comprising at least the predetermined minimal amount/concentration of cannflavin A, on subjects suffering from anxiety (Example 8).
  • Period 1 is for evaluation of the baseline.
  • Periods 2-3 is for evaluation of the cannflavin A treatment against the placebo.
  • the terms "subject”, “patient” or “individual” may be used interchangeably and generally refer to a human, although the methods of the invention are not necessarily limited to humans and should be useful in other mammals.
  • a cannabis composition comprising a predetermined minimal amount/concentration of cannflavin for use in the treatment of one more condition and/or symptom in a subject in need thereof.
  • the predetermined minimal amount/concentration of cannflavin is at least 40ug cannflavin, per daily dose; and in other embodiments, the predetermined minimal amount/concentration of cannflavin is at least 60ug cannflavin, per daily dose.
  • a method for treating various conditions and/or symptoms in a subject in need thereof comprising: selecting, from a plurality of optional cannabis compositions, a suitable cannabis composition, the suitable cannabis composition characterized by containing a predetermined minimal amount/concentration of cannflavin and administering a therapeutically effective amount of the suitable cannflavin composition to the subject.
  • treating refers to an approach for obtaining beneficial or desired results, including clinical results.
  • beneficial or desired clinical results can include, but are not limited to, alleviation or amelioration of one or more symptoms or conditions, diminishment of the extent of a disease or of a condition and/or symptom, stabilization of the state of a disease or a condition and/or symptom, prevention of deterioration of the disease or condition, delay or slowing of disease progression, amelioration or palliation of the condition and/or symptom state, and remission (whether partial or total).
  • the terms “disease”, “condition” and “indication” may be interchangeably used.
  • condition and/or symptom refers to any one of the indications for which treatment efficacy was herein exemplified to positively correlate with cannflavin concentrations. These include sleep difficulties/insomnia, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • condition and/or symptom condition and/or symptoms the invention relate thereto
  • variant conditions and/or symptoms of the invention may be interchangeably used.
  • the term “selecting” or “selection” may refer to choosing from a plurality of options or choosing a product according to it fulfilling a certain requirement, here a minimal cannflavin concentration.
  • the selection comprises selecting according to a product specification that outlines the amount/concentration of the cannabinoids or other compounds found in the product.
  • the selecting comprises measuring/evaluating the concentration of the cannabis-related compound, for example using HPLC.
  • the selecting comprises selecting a composition having a suboptimal concentration/amount of a desired cannabinoid, here cannflavin, and adding to the composition the cannflavin (for example, by adding isolated and/or synthetic cannflavin) so as to achieve the desired concentration/amount.
  • the term “plurality” may refer to two or more, three or more, five or more, or ten or more. Each possibility is a separate embodiment.
  • the term “cannabis composition” may broadly refer to any product having cannabis as a major constituent.
  • the cannabis composition may be a cannabis product suitable for medical use (medical grade).
  • the cannabis composition comprises cannflavin, THC and/or CBD as well as one or more additional cannabinoid or other compounds, such as terpenoids and flavonoids including CBN.
  • the cannabis composition may be raw cannabis, such as buds, inflorescence, or resins.
  • the cannabis composition may be cannabis extract or cannabis oil.
  • the cannabis composition may include standardized extracts.
  • the cannabis composition may be a composition (e.g., a pharmaceutical composition) including one or more isolated cannflavin (in addition to THC and/or CBD).
  • the composition may be in the form of a liquid, a powder, a tablet, a capsule or any other suitable form.
  • the cannabis composition may include one or more natural cannflavin, including one or more extracted cannflavin, one or more isolated cannflavin, and one or more purified cannflavin, or one or more synthetic cannflavin, or any combination thereof. Each possibility is a separate embodiment.
  • optional cannabis composition may refer to a line of actual cannabis products/composition/standardized formulations/extracts between which one can choose.
  • the optional cannabis compositions may be theoretical compositions (e.g. all cannabis composition known and/or available).
  • suitable cannabis composition refers to a cannabis composition which can be chosen for use because it fulfils certain requirements that are not fulfilled by all the potential cannabis compositions (whether actual such as the herein disclosedpredetermined minimal amount or theoretical).
  • the suitable cannabis composition comprises a predetermined minimal amount/concentration of cannflain per daily dose.
  • cannabis product may be used interchangeably, and may all refer to the cannabis composition of the present disclosure.
  • cannflavin refers to a group/family of chemical compounds found in cannabis sativa and includes cannflavin A, cannflavin B, and cannflavin C.
  • cannflavin may refer to any one of cannflavin A, cannflavin B, and cannflavin C, or to any combination thereof, while for example, the term “cannflavin A” refers directly and only to cannflavin A.
  • cannflavin may include natural and synthetic cannflavin.
  • the cannflavin includes cannflavin A, cannflavin B, cannflavin C, or any combination thereof. Each possibility is a separate embodiment.
  • the cannflavin is selected from cannflavin A, cannflavin B, and/or cannflavin C. According to some embodiments, the cannflavin is selected from cannflavin A, cannflavin B, and/or cannflavin C, preferably cannflavin A.
  • the cannflavin is cannflavin A.
  • the at least one cannflavin of the composition may be in the form of an extract including the cannflavin, a purified or distilled cannflavin, or combination of cannflavin derived from an extract, or a combination of cannflavin synthetically produced.
  • cannabinoid refers hereinafter to a class of diverse chemical compounds that act on cannabinoid receptors present in cells that repress neurotransmitter release in the brain.
  • Cannabinoid compounds may include the endocannabinoids (produced naturally in the body by humans and animals), the phytocannabinoids (found in cannabis and some other plants), and synthetic cannabinoids.
  • the at least one cannabinoid of the composition may be in the form of an extract including the cannabinoid, a purified or distilled cannabinoid, or combination of cannabinoids derived from an extract, or a cannabinoid or combination of cannabinoids synthetically produced.
  • synthetic refers to a chemically synthesized cannflavin molecule.
  • an extracted cannflavin molecule may also include additional components (e.g. additional terpenoids, flavonoids or cannabinoids), which are added to the composition, but which are not necessarily required as part of the plant/extract used in the composition.
  • additional components e.g. additional terpenoids, flavonoids or cannabinoids
  • the extracted molecule(s) may be a cannabis plant extract, or it may be extracted from other plant source, including a plant genetically modified to include/express the molecule(s).
  • the extracted molecule(s) may be used as the main extract for the production of cannabis composition/formulation of the present invention, or the extracted molecule(s) may be added to the cannabis composition/formulation/extract of the present invention.
  • the term “isolated” refers to cannflavin molecules which are extracted from a natural resource, so as to become a major component of the extracted mixture.
  • the extracted mixture may also include smaller amounts of other molecules.
  • isolated cannflavin refers to an extract of mixture containing mostly cannflavin, e.g. at least about 50%, at least about 60%, at least about 70% at least about 80% or at least about 90% cannflavin. Each possibility is a separate embodiment.
  • purified refers to cannflavin molecules which are isolated from a natural source, and purified so as to become the essentially only component, i.e. other components are present in residual amounts only.
  • purified cannflavin refers to an extract containing essentially only cannflavin, e.g. less than about 10% or less than about 5% less than about 2% of other molecules or less than about 1% of other molecules. Each possibility is a separate embodiment.
  • administering includes routes of administration which allow the compositions of the invention to perform their intended function.
  • routes of administration include, but not necessarily limited to, smoking, vaporization, inhalation, nasal and/or buccal spraying, drops administered orally or nasally, oral administration (e.g., of tablets or capsules), topical administration, transdermal administration, parenteral administration or the like.
  • the cannabis composition may include a physiologically acceptable vehicle or carrier and optional excipients, adjuvants and preservatives suitable for the route of administration.
  • suitable carriers include, for example, aqueous or alcoholic/aqueous solutions, emulsions or suspensions, including saline and buffered media, sterile water, creams, ointments, lotions, oils, pastes and solid carriers.
  • the herein disclosed cannabis composition comprises a predetermined minimal amount/concentration of cannflavin.
  • the term “predetermined minimal amount/concentration” refers to the content of cannflavin herein found, and exemplified throughout Examples 1-6, to positively correlate with efficacious treatment of the various conditions and/or symptoms the invention relate thereto.
  • the predetermined amount/concentration is the minimal amount required for efficacious treatment and was set, in some embodiments, as: a minimal dose of at least 39.9 ug/day (rounded to 40ug/day) determined based on the 50% percentile, which corresponds to 0.012% (w/w), and considering minimal consumption of 0.333 grams /per day by a subject (i.e., about 1.2 miligrams per month); or in other some embodiments, as: a minimal dose of at least 59ug/day (rounded to 60 ug/day) determined based on the 75% percentile, which corresponds to 0.018% (w/w), and considering minimal consumption of 0.333 grams/per day by a subject (i.e., about 1.8 miligrams per month).
  • the predetermined minimal amount of cannflavin may be any dose of cannflavin (ug/day) determined based on, and corresponding to, at least the 50% percentile, as it was determined in Examples 1-6.
  • the predetermined minimal amount of cannflavin includes any dose of cannflavin (ug/day) determined based on, and corresponding to: at least the 50% percentile, at least the 55% percentile, at least the 60% percentile, at least the 65% percentile, at least the 70% percentile, at least the 75% percentile, at least the 80% percentile, at least the 85% percentile, at least the 90% percentile, at least the 95% percentile, at least the 99% percentile, at least the 100% percentile, or more.
  • cannflavin ug/day
  • the predetermined minimal amount of cannflavin may be between the 50% percentile and the 100% percentile, corresponding to 40ug/day and 144 ug/day (rounded to 145 ug/day).
  • the predetermined minimal amount of cannflavin may include for example, but is not limited to, cannflavin amount/concentrations that are determined based, and corresponding to, ranges between about the 50% percentile and the about 95% percentile, between about the 50% percentile and the about 90% percentile, between about the 50% percentile and the about 85% percentile, or between about the 50% percentile and the about 80% percentile.
  • cannflavin amount/concentrations that are determined based, and corresponding to, ranges between about the 50% percentile and the about 95% percentile, between about the 50% percentile and the about 90% percentile, between about the 50% percentile and the about 85% percentile, or between about the 50% percentile and the about 80% percentile.
  • the predetermined amount/concentration defines the minimal threshold of cannflavin concentrations found to be essential for efficacious treatment having consistent and steady therapeutic effect for various conditions and/or symptoms across a wide range of patients, and it should not be considered as limiting the content of cannflavin in the disclosed compositions and standardized extracts of the invention. Accordingly, it is described herein below that, in some embodiment, the cannabis composition comprises a content of cannflavin of up to about 500,000ug, per daily dose, or in other words, in some embodiment, the cannabis composition comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug, per daily dose.
  • the cannabis composition of the invention comprising a certain predetermined minimal amount/concentration that may be required to be consumed at cumulative amounts during the day in order for them to reach (i.e., administer the subject with) the predetermined minimal amount/concentration per daily dose of composition/product, thereby facilitating the benefits of the treatment that consistently alleviate/attenuate several conditions and/or symptoms.
  • predetermined amount/concentration and “predetermined minimal amount/concentration” may be interchangeably used.
  • the predetermined minimal amount of cannflavin includes at least about 40ug of cannflavin per daily dose unit, at least about 45ug of cannflavin per daily dose unit, at least about 50ug of cannflavin per daily dose unit, at least about 55ug of cannflavin per daily dose unit, at least about 60ug of cannflavin per daily dose unit, at least about 70ug of cannflavin per daily dose unit, at least about 80ug of cannflavin per daily dose unit, at least about 90ug of cannflavin per daily dose unit, at least about lOOug of cannflavin per daily dose unit, at least about 1 lOug of cannflavin per daily dose unit, at least about 120ug of cannflavin per daily dose unit, at least about 130ug of cannflavin per daily dose unit, or at least about 140ug of cannflavin per daily dose unit .
  • Each possibility is a separate embodiment.
  • the predetermined minimal amount of cannflavin comprises between about 40ug and about 145ug of cannflavin per daily dose unit, between about 40ug and about 120ug of cannflavin per daily dose unit, between about 40ug and about lOOug of cannflavin per daily dose unit, between about 40ug and about 90ug of cannflavin per daily dose unit, between about 60ug and about 145ug of cannflavin per daily dose unit, between about 60ug and about 120ug of cannflavin per daily dose unit, between about 60ug and about lOOug of cannflavin per daily dose unit, between about 60ug and about 90ug of cannflavin per daily dose unit, between about 40ug and about 80ug of cannflavin per daily dose unit, or between about 40ug and about 60ug of cannflavin per daily dose unit.
  • the term “daily dose” refers to an amount that is consumed per day. In some of the herein disclosed embodiments, it may be understood with respect to the total (i.e., cumulative) amount of cannflavin to be consumed daily in order to obtain an efficient amelioration of anxiety (e.g., at least 40ug/day or at least 60ug/day). In some of the herein disclosed embodiments, it may also be understood with respect to the cannabis composition/product referring to the actual total dosage a subject consumes from the cannabis product per day (or to the total dosage that is recommended to the subject to consume per day) in order to ensure that the dosage includes a minimal amount of at least 40ug or at least 60ug cannflavin.
  • a cannabis composition/product prepared, according to the non-limiting standardized extracts of formulas 1-4 (in Example 9), contain 0.005% or 0.01% cannflavin, that correspond to 0.05mg cannflavin and O.lmg cannflavin per 1g of cannabis product.
  • a subject that is recommended to consume 0.8g per day of these cannabis products is administered with a daily amount of 40ug and 80ug of cannflavin, respectively.
  • An effective amount of the cannabis composition and the daily dose, necessary to achieve a therapeutic effect may vary according to factors such as the age, sex, and weight of the subject. Dosage regimens can be adjusted to provide the optimum therapeutic response.
  • the predetermined amount/concentration defines the minimal threshold of cannflavin concentrations advantageously and surprisingly found to be essential for efficacious treatment that encompasses a steady therapeutic effect of ameliorating/alleviating several conditions and/or symptoms, and it should not be considered as limiting the content of cannflavin in the disclosed compositions and standardized extracts of the invention.
  • the cannabis composition comprises a maximal amount/concentration of cannflavin of about 500,000ug, per daily dose.
  • the maximal amount/concentration of cannflavin in the cannabis composition/suitable composition/standardized extract is about 500,000ug per daily dose, about 400,000ug per daily dose, about 350,000ug per daily dose, about 300,000ug per daily dose, about 250,000ug per daily dose, about 200,000ug per daily dose, about 150,000ug per daily dose, about 100,000ug per daily dose, about 80,000ug per daily dose, about 60,000ug per daily dose, about 40,000ug per daily dose, about 30,000ug per daily dose, about 20,000ug per daily dose, about 15,000ug per daily dose, about 10,000ug per daily dose, about 7,500ug per daily dose, about 5,000ug per daily dose, about 2,500ug per daily dose, about l,500ug per daily, about l,250ug per daily dose, about l,000ug per daily dose, about 900ug per daily dose, about 800ug per daily dose, about 700ug per daily dose, about 600ug per daily dose, about
  • the cannabis composition comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug, per daily dose.
  • the cannabis composition comprises a content of cannflavin between the predetermined minimal amount/concentration and any one of the maximum amount/concentration of: about 500,000ug per daily dose, about 400,000ug per daily dose, about 350,000ug per daily dose, about 300,000ug per daily dose, about 250,000ug per daily dose, about 200,000ug per daily dose, about 150,000ug per daily dose, about 100,000ug per daily dose, about 80,000ug per daily dose, about 60,000ug per daily dose, about 40,000ug per daily dose, about 30,000ug per daily dose, about 20,000ug per daily dose, about 15,000ug per daily dose, about 10,000ug per daily dose, about 7,500ug per daily dose, about 5,000ug per daily dose, about 2,500ug per daily dose, about l,500ug per daily, about l,250ug per daily dose, about l,000ug per daily dose, about 900ug per daily dose, about 800ug per daily dose, about 700ug per daily dose, about 300
  • the cannabis composition may comprise a content of cannflavin between the predetermined minimal amount/concentration of any one of about 40/50/60/80/90/100/120 or 140ug/day, and the maximum amount/concentration of 500,000ug/day; and in some embodiments, the cannabis composition may comprise a content of cannflavin between the predetermined minimal amount/concentration of any one of 40/50/60/80/90/100/120 or 140ug/day, and the maximum amount/concentration of 175ug/day.
  • Each possibility is a separate embodiment.
  • the herein disclosed cannabis composition comprises at least a minimal amount/concentration of cannflavin; according to some embodiments, the herein disclosed cannabis composition comprises cannflavin at a concentration of at least 40ug per daily dose; according to some embodiments, the herein disclosed cannabis composition comprises at least 40ug of cannflavin.
  • the cannabis composition is enriched with cannflavin.
  • the term ’’enriched refers to a cannabis composition and standardized extracts including cannflavin at amount/concentration of more than 2 times the predetermined minimal amount/concentration of cannflavin (i.e., at least 80ug per daily dose), and is limited only by the maximum amount/concentration of about 500,000ug per daily dose.
  • the cannabis composition enriched with cannflavin comprises at least 2 times, sometimes at least 4, or at least 10 times, or sometimes at least about 30 times, or at least about 100 times, sometimes at least about 200 times the predetermined minimal amount/concentration of cannflavin, sometimes at least about 500 times the predetermined minimal amount/concentration of cannflavin, or sometimes at least about 2000 times the predetermined minimal amount/concentration of cannflavin, or more.
  • Each possibility is a separate embodiment.
  • the composition comprises cannflavin at maximal amount/concentration of less than 5.0000%.
  • the composition comprises cannflavin at maximal concentration of less than 5.0000%, less than 4.0000%, less than 3.0000%, less than 2.0000%, less than 1.0000%, less than 0.9000%, less than 0.8000%, less than 0.7000%, less than 0.6000%, less than 0.5000%, less than 0.4000%, less than 0.3000%, less than 0.2000%, less than 0.1000%, or less.
  • cannflavin at maximal concentration of less than 5.0000%, less than 4.0000%, less than 3.0000%, less than 2.0000%, less than 1.0000%, less than 0.9000%, less than 0.8000%, less than 0.7000%, less than 0.6000%, less than 0.5000%, less than 0.4000%, less than 0.3000%, less than 0.2000%, less than 0.1000%, or less.
  • the maximal concentration of cannflavin in the composition is less than about 0.099%, less than about 0.095%, less than about 0.094%, less than about 0.093%, less than about 0.092%, less than about 0.091%, less than about 0.090%, less than about 0.080%, less than about 0.070%, less than about 0.060%, less than about 0.050%, less than about 0.040%, less than about 0.035%, less than about 0.030%, less than about 0.025%, less than about 0.020%, less than about 0.015%, less than about 0.010%, less than about 0.009%, less than about 0.008%, less than about 0.007%, less than about 0.006%, less than about 0.005%, or less than about 0.001%, or less than about 0.0005%.
  • Each possibility is a separate embodiment.
  • the maximal concentration of cannflavin in the composition is between about 5.0000% and about 0.00001%, between about 0.50000% and about 0.0001%, between about 0.05000% and about 0.001%, between about 0.00500% and about 0.00100%, between about 1.0000% and about 0.00001%, between about 0.10000% and about 0.0001%, between about 0.01000% and about 0.001%.
  • the maximal concentration of cannflavin in the composition is between about 5.0000% and about 0.6000% between about 5.0000% and about 1.0000%, between about 3.0000% and about 1.0000%, or between about 2.0000% and about 0.6000%.
  • the maximal concentration of cannflavin in the composition is between about 0.095% and about 0.00001%, between about 0.095% and about 0.0001%, between about 0.095% and about 0.001%, or between about 0.095% and about 0.010%.
  • the maximal concentration of cannflavin in the composition is between about 0.095% and about 0.00001%, between about 0.095% and about 0.0001%, between about 0.095% and about 0.001%, or between about 0.095% and about 0.010%.
  • the composition contains cannflavin as the only cannabis-derived compound.
  • the composition contains cannflavin with THC, and/or CBD as the only cannabinoids.
  • the composition comprises THC, CBD, and cannflavin.
  • the composition comprising THC, CBD, and cannflavin further comprises at least one additional cannabinoid, for example CBN.
  • the disclosed cannabis composition can be further characterized by a minimal ratio (%) of cannflavin and THC concentrations (cannflavin/THC ratio (%)).
  • the cannflavin and THC concentrations are characterized by a ratio of at least about 0.070%.
  • the cannflavin and THC concentrations are characterized by a ratio of at least about 0.06%, at least about 0.07%, at least about 0.08%, at least about 0.085%, at least about 0.09%, at least about 0.10%, at least about 0.11%, at least about 0.12%, at least about 0.15%, at least about 0.20%, at least about 0.25%, at least about 0.30%, at least about 0.35%, at least about 0.45%, at least about 0.50%, at least about 0.60%, at least about 0.70%, at least about 0.90%, at least about 1.00%, at least about 5.00%, at least about 10.00%, at least about 25.00%, at least about 50.00%, at least about 75.00%, at least about 100.00%, at least about 500.00%, or more.
  • Each possibility is a separate embodiment.
  • the cannflavin and THC concentrations are characterized by a ratio of between about 0.06% and about 1000.00%, a ratio of between about 0.06% and about 500.00%, a ratio of between about 0.06% and about 100.00%, a ratio of between about 0.06% and about 25.00%, between about 0.06% and about 10.00%, between about 0.06% and about 5.00%, or between about 0.06% and about 1.00%, between about 0.06% and about 0.50%, or between about 0.06% and about 0.20%.
  • a ratio of between about 0.06% and about 1000.00% a ratio of between about 0.06% and about 500.00%, a ratio of between about 0.06% and about 100.00%, a ratio of between about 0.06% and about 25.00%, between about 0.06% and about 10.00%, between about 0.06% and about 5.00%, or between about 0.06% and about 1.00%, between about 0.06% and about 0.50%, or between about 0.06% and about 0.20%.
  • Each possibility
  • the disclosed cannabis composition may be further characterized by a minimal ratio (%) of cannflavin and CBD concentrations (cannflavin/CBD ratio (%)).
  • the cannflavin and CBD concentrations are characterized by a ratio of at least 27%. In some embodiments, the cannflavin and CBD concentrations are characterized by a ratio of at least 29%, at least 31%, at least 32%.
  • the cannflavin and CBD concentrations are characterized by a ratio of at least about 0.20%, at least about 1.00%, at least about 5.00%, at least about 7.50%, at least about 10.0%, at least about 25.0%, at least about 30.0%, at least about 50.0%, at least about 75.0%, at least about 100%, at least about 250%, at least 500%, at least about 750%, at least about 1000%, at least about 5000%, at least about 10,000%, at least about 100,000%, or more.
  • Each possibility is a separate embodiment
  • the cannflavin and CBD concentrations are characterized by a ratio of between about 0.20% and about 200,000.0%, a ratio of between about 30% and about 500,000.0%, between about 27% and about 200,000.0%, a ratio of between about 30% and about 50,000.0%, a ratio of between about 30% and about 20,000.0%, a ratio of between about 30% and about 10,000.0%, a ratio of between about 30% and about 1,000.0%, a ratio of between about 1.0% and about 2000.0%, a ratio of between about 10% and about 2000.0%, between about 1.0% and about 500.00%, or between about 1.0% and about 100%.
  • a ratio of between about 0.20% and about 200,000.0% a ratio of between about 30% and about 500,000.0%, between about 27% and about 200,000.0%, a ratio of between about 30% and about 50,000.0%, a ratio of between about 30% and about 20,000.0%, a ratio of between about 30% and about 10,000.0%, a ratio of between about 30% and about 1,000.0%, a ratio
  • the cannabis composition comprises raw cannabis.
  • At least a portion of the cannflavin in the composition comprises extracted, isolated, purified, and/or synthetic cannflavin, or any combination thereof.
  • each possibility is a separate embodiment.
  • At least a portion of the cannflavin in the composition comprises isolated and/or synthetic cannflavin. Each possibility is a separate embodiment.
  • the composition is selected from a plurality of potential cannabis compositions based on an analysis of the content of cannflavin in the plurality of potential cannabis compositions.
  • cannflavin is added to the composition if the cannflavin content is below the predetermined minimal amount/concentration.
  • At least a portion of the cannflavin added to the composition comprises isolated and/or synthetic cannflavin. Each possibility is a separate embodiment.
  • the composition is selected based on an analysis/evaluation of the content of cannflavin in the plurality of cannabis compositions. According to some embodiments, based on the analysis of the content cannflavin is added to the composition to reach the predetermined minimal content, or above. According to some embodiments cannflavin is added to the composition if the content of cannflavin measured is below a predetermined minimal amount/concentration.
  • administration of the cannabis composition comprises administering by route of smoking, inhalation, vaporization, oral administration, buccal administration, nasal administration, topical administration, transdermal administration parenteral administration, or any combination thereof.
  • a combination of cannflavin at the minimum predetermined concentration of at least 40ug/day and CBN at minimal concentration of at least 825pg/day predicts/correlates with treatment efficacy of one or more of the conditions and/or symptoms, including but not limited to pain.
  • the cannabis composition or the standardized extract comprises cannflavin at least at its minimal predetermined amount/concentration and additionally CBN at minimal concentration of at least 825 pg per daily dose.
  • the cannabis composition further comprises CBN at minimal concentrations of at least 825pg/day. According to some embodiments, the cannabis composition further comprises CBN at concentrations of at least 1075pg/day.
  • the cannabis composition further comprises CBN at a minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose or more.
  • CBN at a minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose or more.
  • the cannabis composition further comprises CBN at a maximal concentration of about 600,000ug per daily dose.
  • the cannabis composition further comprises CBN at an amount between any one of the minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose and a maximal concentration of about 600,000ug per daily dose.
  • CBN at an amount between any one of the minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose and a maximal concentration of about 600,000ug per daily dose.
  • Each possibility is a separate embodiment.
  • the minimal amount of CBN includes any dose of CBN (ug/day) determined based on, and corresponding to: at least the 50% percentile, at least the 55% percentile, at least the 60% percentile, at least the 65% percentile, at least the 70% percentile, at least the 75% percentile, at least the 80% percentile, at least the 85% percentile, at least the 90% percentile, at least the 95% percentile, at least the 99% percentile, at least the 100% percentile, or more.
  • CBN ug/day
  • the cannabis composition further comprises CBN at an amount of at least about 825ug/day for use in treating one or more condition and/or symptom, including sleep disorder, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • condition and/or symptom including sleep disorder, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • the cannabis composition further comprises total CBN at an amount of at least about 825ug for use in treating pain.
  • the pain includes, but is not limited to, chronic and/or acute pain of one or more of: orthopedic pain, muscles pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof.
  • orthopedic pain muscles pain
  • spinal disc herniation pain neuropathic pain
  • widespread pain abdominal pain, and/or headaches, or any combination thereof.
  • headaches or any combination thereof.
  • CBN is added to the cannabis composition or the standardized extract.
  • CBN is added to the cannabis composition or the standardized extract at a minimal amount of at least 825ug/day or at least 1075ug/day.
  • CBN is added to the cannabis composition or the standardized extract when CBN amounts are below a minimal concentration of at least 825ug/day.
  • e composition comprises extracted, isolated, purified, and/or synthetic CBN, or any combination thereof. Each possibility is a separate embodiment.
  • At least a portion of the CBN added to the composition comprises isolated and/or synthetic CBN.
  • isolated and/or synthetic CBN are separate embodiments.
  • the composition may be characterized by a CBN to THC ratio.
  • the median of this ratio (about 1.3%) can be considered as minimum ratios of CBN to THC needed for the efficacious treatment.
  • the composition may be characterized by a CBN to THC ratio of at least about 1.5%, at least about 10%, at least about 50%, at least about 100%, at least about 500%, at least about 1000%, at least about 2000%, at least about 5000%, or more. Each possibility is as separate embodiment.
  • the composition may be characterized by a CBN to THC ratio of between about 1.5% and about 20,000%, between about 1.5% and about 15,000% between about 1.5% and about 10,000%, between about 1.5% and about 5,000%, between about 1.5% and about 2,000%, between about 1.5% and about 1,000%, between about 1.5% and about 500%, or between about 1.5% and about 100%.
  • a CBN to THC ratio of between about 1.5% and about 20,000%, between about 1.5% and about 15,000% between about 1.5% and about 10,000%, between about 1.5% and about 5,000%, between about 1.5% and about 2,000%, between about 1.5% and about 1,000%, between about 1.5% and about 500%, or between about 1.5% and about 100%.
  • the composition may be characterized by a CBN to CBD ratio.
  • the median of these ratio (about 414%) can be considered as minimum ratios of CBN to CBD needed for the efficacious treatment.
  • the composition may be characterized by a CBN to THC ratio of at least about 415%, at least about 500%, at least about 1,000%, at least about 2,000%, at least about 5,000%, at least about 10,000%, at least about 50,000%, at least about 100,000%, or more. Each possibility is as separate embodiment.
  • the composition may be characterized by a CBN to THC ratio of between about 415% and about 200,000%, between about 415% and about 50,000% between about 415% and about 20,000% between about 415% and about 10,000% between about 415% and about 5,000%, or between about 415% and about 1,000%.
  • CBN to THC ratio of between about 415% and about 200,000%, between about 415% and about 50,000% between about 415% and about 20,000% between about 415% and about 10,000% between about 415% and about 5,000%, or between about 415% and about 1,000%.
  • the composition may also be characterized by a minimal cannflavin to CBN ratio considered as minimum ratio needed for the efficacious treatment.
  • the one more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof. Each possibility is a separate embodiment.
  • condition and/or symptom includes sleep difficulties; In some embodiments, the condition and/or symptom includes pain; In some embodiments, the condition and/or symptom includes headaches; In some embodiments, the condition and/or symptom includes abdominal pain; In some embodiments, the condition and/or symptom includes anxiety.
  • at least one condition and/or symptom is characterized by a high level of perceived severity. In some embodiments, the high level of perceived severity comprises self-reported ranking of 4 or 5 on a scale of 1-5.
  • severity refers to the perceived severity of the condition and/or symptom as were self-reported on a scale of 1-5 by patients in questionnaires, as exemplified throughout Examples 1-6. Accordingly, a high level of severity includes self- reported ranking of 4 or 5 out of 5.
  • condition and/or symptom is a comorbid condition and/or symptom associated with at least one additional medical condition; In some embodiments, the condition and/or symptom is a comorbidity associated with at least one additional medical condition.
  • condition and/or symptom or “comorbidity” or “comorbidity associated with at least one additional medical condition” refers to one or more of the condition and/or symptom of the present invention including sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof, when these simultaneously exist with (i.e., co-exist with or associated with or in comorbidity with) at least one other/additional medical condition in the same patient (or population of patients), and regardless of their causal relationship (i.e., dependent or independent).
  • comorbidity refers to a condition and/or symptom that is associated with at least one additional medical condition.
  • PTSD Post-Traumatic Stress Disorder
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • cancer pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • the “other/additional medical condition” includes PTSD, FM, IBD, cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • the comorbidity includes at least a condition and/or symptom of the present invention (i.e., sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof) that co-exist/associated in the same patient with one or more additional/other medical condition (e.g., PTSD, FM, IBD cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof).
  • a condition and/or symptom of the present invention i.e., sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof
  • additional/other medical condition e.g., PTSD, FM, IBD cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • Additional non-limiting examples of other/additional medical condition that may coexist with one or more condition and/or symptom of the present invention include: depression, anxiety, neurodegenerative diseases (such as multiple system atrophy (MSA), Parkinson's disease (PD) and Lewy body disease (LBD) or Alzheimer's disease (AD)), Schizophrenia, Bipolar disorder, and iron-deficiency anemia.
  • MSA multiple system atrophy
  • PD Parkinson's disease
  • LBD Lewy body disease
  • AD Alzheimer's disease
  • Schizophrenia Bipolar disorder
  • Bipolar disorder iron-deficiency anemia
  • the comorbidity of a certain condition and/or symptom of the present invention which may be associated with one or more additional medical condition includes: a comorbidity that occurs within the same patient independently of each other condition; as well as a comorbidity that occurs within the same patient with some relation or causality between conditions (i.e., dependent).
  • the comorbidity includes one or more of: sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof, associated with at least one other/additional medical condition.
  • sleep difficulties pain, headaches, abdominal pain and anxiety, or any combination thereof, associated with at least one other/additional medical condition.
  • the comorbidity includes one or more of sleep difficulties, pain and abdominal pain, or any combination thereof, associated with at least one other/additional medical condition.
  • sleep difficulties pain and abdominal pain, or any combination thereof, associated with at least one other/additional medical condition.
  • pain and abdominal pain or any combination thereof, associated with at least one other/additional medical condition.
  • At least one of the conditions and/or symptoms includes a comorbidity associated with at least one additional medical condition; and wherein the at least one additional medical condition includes Post-Traumatic Stress Disorder (PTSD), fibromyalgia (FM), Inflammatory Bowel Disease (IBD), cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • Post-Traumatic Stress Disorder PTSD
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • cancer pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • condition and/or symptom includes sleep difficulties.
  • the sleep difficulties include, but are not limited to one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep ‘light sleep’, fragmented/impaired sleep, difficulty waking up, sleepiness, and insufficient sleep, or any combination thereof. Each possibility is a separate embodiment. In some embodiments, the sleep difficulties are selected from one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep ‘light sleep’, fragmented/impaired sleep, and insufficient sleep, or any combination thereof. Each possibility is a separate embodiment.
  • the sleep difficulties are selected from one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep ‘light sleep’, fragmented/impaired sleep, and insufficient sleep, movements of legs or limbs during sleep, abnormal contraction muscle tonus during sleep, disordered/abnormal breathing/respiration during sleep, and snoring, or any combination thereof.
  • difficulty in falling asleep difficulty in maintaining continuous sleep
  • having low-quality sleep ‘light sleep’ fragmented/impaired sleep
  • fragmented/impaired sleep fragmented/impaired sleep
  • insufficient sleep movements of legs or limbs during sleep, abnormal contraction muscle tonus during sleep, disordered/abnormal breathing/respiration during sleep, and snoring, or any combination thereof.
  • Each possibility is a separate embodiment.
  • sleep difficulties include a sleep disorder.
  • sleep disorder may be interpreted in its broad meaning and herein refers to a condition characterized by having sleep difficulties such as insomnia.
  • the sleep disorder includes but is not limited to insomnia and/or circadian rhythms sleep-wake phase disorder (SWPD), including advanced phase and/or delayed phase.
  • SWPD sleep-wake phase disorder
  • the sleep disorder is selected from one or more of: Insomnia, circadian rhythms advanced sleep-wake phase disorder (ASWPD), and circadian rhythms delayed sleep-wake phase disorder (DSWPD), or any combination thereof. Each possibility is a separate embodiment.
  • the sleep disorder includes insomnia.
  • sleep difficulties include insomnia.
  • the sleep disorder is selected from one or more of: Insomnia, Parasomnias, circadian rhythms advanced sleep-wake phase disorder (ASWPD), circadian rhythms delayed sleep-wake phase disorder (DSWPD), sleep disordered breathing (SDB) sleep apnea (SA), obstructive sleep apnea (OSA), rapid-eye movement (REM) behavior disorder, non-rapid-eye movement parasomnia (NREM parasomnia), restless legs syndrome (RLS), periodic limb movement of sleep (PLMS), Bruxism, Nocturia, Sleepwalking, Snoring, and Narcolepsy, or any combination thereof.
  • ASWPD circadian rhythms advanced sleep-wake phase disorder
  • DSWPD circadian rhythms delayed sleep-wake phase disorder
  • SDB sleep disordered breathing
  • SA sleep apnea
  • OSA obstructive sleep apnea
  • REM rapid-eye movement
  • NREM parasomnia non-rapi
  • sleep difficulties is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition includes Post-Traumatic Stress Disorder (PTSD), fibromyalgia (FM), Inflammatory Bowel Disease (IBD), cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • Post-Traumatic Stress Disorder PTSD
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • cancer pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • sleep difficulties is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition includes Post-Traumatic Stress Disorder PTSD, fibromyalgia (FM) and/or cancer, or any combination thereof.
  • the at least one additional medical condition includes Post-Traumatic Stress Disorder PTSD, fibromyalgia (FM) and/or cancer, or any combination thereof.
  • sleep difficulties is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition includes Post-Traumatic Stress Disorder (PTSD).
  • PTSD Post-Traumatic Stress Disorder
  • condition and/or symptom includes pain
  • the pain includes, but is not limited to, one or more of: orthopedic pain, muscles pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof. Each possibility is a separate embodiment.
  • pain refers to persistent pain that lasts for an extended period or to acute pain, each separately and combined.
  • the pain may include chronic pain and/or acute pain.
  • orthopedic pain may be chronic and/or acute
  • muscles pain may be chronic and/or acute
  • spinal disc herniation pain may be chronic and/or acute
  • neuropathic pain may be chronic and/or acute
  • widespread pain may be chronic and/or acute.
  • the pain includes, but is not limited to, one or more of: orthopedic pain, muscles pain, spinal disc herniation pain, neuropathic pain, and/or widespread pain, or any combination thereof.
  • pain is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition includes fibromyalgia (FM), Inflammatory Bowel Disease (IBD) and/or cancer, or any combination thereof.
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • cancer or any combination thereof.
  • condition and/or symptom includes abdominal pain.
  • abdominal pain is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition includes fibromyalgia (FM) and/or Inflammatory Bowel Disease (IBD).
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • the condition and/or symptom includes headaches.
  • headache is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition.
  • the condition and/or symptom includes anxiety.
  • anxiety is a comorbid condition and/or symptom associated with at least one additional medical condition; and wherein the at least one additional medical condition includes fibromyalgia (FM) and/or cancer.
  • FM fibromyalgia
  • anxiety should be interpreted in its broad medical meaning.
  • anxiety may refer to “anxiety disorders” such as, but not limited to, Generalized Anxiety Disorder (GAD), Social Anxiety Disorder (SAD), Panic Disorder (PD) and/or a phobia (such as but, not limited to, agoraphobia), as defined per DSM 5; or in some other embodiments, the term “anxiety” may refer to a state of high stress (distress) with anxiety levels within normative, non-pathological range.
  • GAD Generalized Anxiety Disorder
  • SAD Social Anxiety Disorder
  • PD Panic Disorder
  • a phobia such as but, not limited to, agoraphobia
  • the cannabis composition comprises a standardized extract.
  • annabis extract refers to an herbal preparation prepared by extraction of cannabis plant material.
  • extraction of a cannabis extract may be achieved by various techniques, including but not limited to using solvents, like alcohols or other organic solvents, gasses like CO2 and butane, and/or to physical methods like presses and extruders. Each possibility is a different embodiment.
  • the herein disclosed cannabis composition may comprise such a standardized extract in some embodiments thereof, and in some embodiments the herein disclosed cannabis composition may refer to such a standardized extract.
  • standardized extract and “standardized cannabis extract” may be interchangeably used and refer to a cannabis extract formulated/standardized to include (by addition) at least a certain amount/content of one or more active ingredient, such as but not limited to: cannabinoids like THC, CBD, or cannflavin.
  • the standardized extract may refer to a cannabis extract from a natural source formulated/standardized to include (by addition) at least a certain amount/content of one or more active ingredient in order to reach a certain minimal amount of that ingredient.
  • the herein disclosed cannabis composition may comprise such a standardized extract in some embodiments thereof, and in some embodiments the herein disclosed cannabis composition may refer to or include such a standardized extract.
  • standardization can be achieved by mixing extracts from different sources and active ingredients ratios, with or without dilution with excipients.
  • standardization can be achieved by adding to the formulation extracted, isolated, purified, and/or synthetic active ingredient.
  • the cannabis extract comprises enriched cannflavin content.
  • the cannabis extract comprises THC rich content.
  • the cannabis extract comprises CBD rich content.
  • the cannabis extract has THC dominance.
  • the cannabis extract has CBD dominance.
  • the cannabis extract has a balanced THC and CBD content.
  • the cannabis extract comprises cannflavin.
  • the cannabis extract comprises CBG rich content.
  • a cannabis extract having a THC rich content may refer to cannabis extracts having a THC content greater by at least about 2 times, at least about 20 times, at least about 50 times, at least about 100 times, or at least about 200 times, than its CBD content.
  • THC content greater by at least about 2 times, at least about 20 times, at least about 50 times, at least about 100 times, or at least about 200 times, than its CBD content.
  • a cannabis extract having a CBD rich content may refer to cannabis extracts having a CBD content greater by at least about 2 times, at least about 20 times, at least about 50 times, at least about 100 times, at least about 200 times, than its THC content. Each possibility is a different embodiment.
  • a cannabis extract with THC dominance may have a THC content greater than its CBD content by between about 1 to about 20 times.
  • a cannabis extract with CBD dominance may have a CBD content greater than its THC content by between about 1 to about 20 times.
  • a cannabis extract with balanced THC and CBD content may comprise contents of THC and CBD within the range of a ratio of THC:CBD 1:2 to a ratio of THC:CBD 2:1.
  • the cannabis composition or the standardized extract comprises at least about 2.6% (w/w) THC, at least about 2.6% (w/w) CBD, at least about 0.005% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • THC at least about 2.6% (w/w) THC
  • CBD at least about 2.6% (w/w) CBD
  • 0.005% w/w
  • cannflavin at least about 0.005% (w/w) cannflavin
  • optionally 0.5% (w/w) Vitamin E optionally 0.5%
  • the cannabis composition or the standardized extract comprises at least about 5.2% (w/w) THC, at least about 5.2% (w/w) CBD, at least about 0.01% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • THC at least about 5.2%
  • CBD at least about 5.2%
  • cannflavin at least about 0.01%
  • cannflavin at least about 0.01%
  • cannflavin optionally 0.5%
  • Vitamin E optionally 0.5%
  • the cannabis composition or the standardized extract comprises THC and/or CBD concentrations of at least about 2.5% (w/w) each, at least about 5.0% (w/w) each, at least about 7.5% (w/w) each, at least about 10% (w/w) each, at least about 12.5% (w/w) each, at least about 15% (w/w) each, at least about 17.5% (w/w) each, at least about 20% (w/w) each, at least about 25% (w/w) each, at least about 30% (w/w) each, or at least about 35% (w/w) each, or at least about 40% (w/w) each, or any combination thereof.
  • THC and/or CBD concentrations of at least about 2.5% (w/w) each, at least about 5.0% (w/w) each, at least about 7.5% (w/w) each, at least about 10% (w/w) each, at least about 12.5% (w/w) each, at least about 15% (w/w) each, at least about 17.5% (w/w)
  • the cannabis composition or the standardized extract comprises THC and/or CBD concentrations of between about 2.5% (w/w) and about 50% (w/w) each, between about 5.0% (w/w) and about 40% (w/w) each, between about 7.5% (w/w) and about 35% (w/w) each, between about 10% (w/w) and about 30% (w/w) each, or between about 15% (w/w) and about 25% (w/w) each, or any combination thereof.
  • THC and/or CBD concentrations of between about 2.5% (w/w) and about 50% (w/w) each, between about 5.0% (w/w) and about 40% (w/w) each, between about 7.5% (w/w) and about 35% (w/w) each, between about 10% (w/w) and about 30% (w/w) each, or between about 15% (w/w) and about 25% (w/w) each, or any combination thereof.
  • the cannabis composition comprises cannabis extracts enriched with cannflavin.
  • the enriched cannabis extract, or the cannabis composition comprising enriched cannabis extracts includes extracted, isolated, purified, or synthetic cannflavin. Each possibility is a separate embodiment.
  • the cannabis extract includes enriched levels of cannflavin from natural source. According to some embodiments, cannabis extract includes enriched levels of cannflavin isolated or purified from a natural source. According to some embodiments, cannabis extract includes enriched levels of synthetic cannflavin.
  • the cannabis extracts enriched with cannflavin comprises at least about 2 times the predetermined minimal amount/concentration of cannflavin.
  • the cannabis extract enriched with cannflavin comprises at least about 200 times the predetermined minimal amount/concentration of cannflavin.
  • a standardized extracts is enriched with cannflavin.
  • a standardized extracts enriched with cannflavin includes an amount/concentration of more than 2 times the predetermined minimal amount/concentration of cannflavin (e.g., at least 80ug per daily dose), and is limited only by the maximum amount/concentration of about 500,000ug per daily dose.
  • the cannabis composition comprises a maximal amount/concentration of cannflavin of about 500,000ug, per daily dose.
  • the maximal amount/concentration of cannflavin in the cannabis composition/suitable composition/standardized extract is about 500,000ug per daily dose, about 400,000ug per daily dose, about 350,000ug per daily dose, about 300,000ug per daily dose, about 250,000ug per daily dose, about 200,000ug per daily dose, about 150,000ug per daily dose, about 100,000ug per daily dose, about 80,000ug per daily dose, about 60,000ug per daily dose, about 40,000ug per daily dose, about 30,000ug per daily dose, about 20,000ug per daily dose, about 15,000ug per daily dose, about 10,000ug per daily dose, about 7,500ug per daily dose, about 5,000ug per daily dose, about 2,500ug per daily dose, about l,500ug per daily, about l,250ug per daily dose, about l,000ug per daily dose, about 900ug per daily dose, about 800ug per daily dose, about 700ug per daily dose, about 600ug per daily dose, about
  • the cannabis composition comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug, per daily dose.
  • the cannabis composition comprises a content of cannflavin between the predetermined minimal amount/concentration and any one of the maximum amount/concentration of: about 500,000ug per daily dose, about 400,000ug per daily dose, about 350,000ug per daily dose, about 300,000ug per daily dose, about 250,000ug per daily dose, about 200,000ug per daily dose, about 150,000ug per daily dose, about 100,000ug per daily dose, about 80,000ug per daily dose, about 60,000ug per daily dose, about 40,000ug per daily dose, about 30,000ug per daily dose, about 20,000ug per daily dose, about 15,000ug per daily dose, about 10,000ug per daily dose, about 7,500ug per daily dose, about 5,000ug per daily dose, about 2,500ug per daily dose, about l,500ug per daily, about l,250ug per daily dose, about l,000ug per daily dose, about 900ug per daily dose, about 800ug per daily dose, about 700ug per daily dose, about 300
  • the composition comprises cannflavin at maximal amount/concentration of less than 5.0000%.
  • the maximal concentration of cannflavin in the composition is between about 5.0000% and about 0.00001%, between about 5.0000% and about 0.6000%, or between about 0.095% and about 0.00001%.
  • each possibility is a separate embodiment.
  • a standardized cannabis extract comprising extracts from a natural source and a predetermined minimal amount/concentration of at least 40ug per daily dose of isolated and/or synthetic cannflavin.
  • natural source refers to a plant source and should be interpreted in its broader sense.
  • a natural source may include a genetically modified, gene edited or transgenic plant.
  • the term “genetically modified” refers to a gene edited plant or a transgenic plant, and include both cannabis plants, and other non-cannabis plants, genetically modified to express/include a cannabinoid at significantly higher concentrations relative to a plant which is not genetically modified.
  • the cannabis plant is a genetically modified cannabis plant.
  • the cannabis composition comprises extracts from a natural source and a significantly higher concentrations of cannflavin purified or isolated from a genetically modified cannabis plant.
  • the cannabis composition or the standardized extract comprising a cannabinoid extracted, purified or isolated from a genetically modified plant comprises a significantly higher concentrations of said extracted, purified or isolated cannabinoid, relative to a same cannabis composition comprising a cannabinoid extracted, purified or isolated from a plant which is not genetically modified.
  • significantly higher concentrations of cannflavin extracted, purified or isolated from a genetically modified source includes concentration at the same ranges of cannabis composition enriched with cannflavin.
  • enriched and “significantly higher concentration” may be interchangeably used, and refer to the same ranges of concentration.
  • the cannabis standardized extract comprises a cannabinoid extracted, purified or isolated from a genetically modified plant.
  • a cannabinoid extracted, purified or isolated from a genetically modified plant Each possibility is a separate embodiment.
  • the cannabis composition comprises a cannflavin extracted, purified or isolated from a genetically modified cannabis plant.
  • the cannabis composition or the standardized extract comprises cannflavin at maximal amount/concentration of less than 5.0000%, less than 4.0000%, less than 3.0000%, less than 2.0000%, less than 1.0000%, less than 0.9000%, less than 0.8000%, less than 0.7000%, less than 0.6000%, less than 0.5000%, less than 0.4000%, less than 0.3000%, less than 0.2000%, less than 0.1000%.
  • Each possibility is a separate embodiment.
  • the maximal concentration of cannflavin in the cannabis composition or standardized extract is less than about 0.099%, less than about 0.095%, less than about 0.094%, less than about 0.093%, less than about 0.092%, less than about 0.091%, less than about 0.090%, less than about 0.080%, less than about 0.070%, less than about 0.060%, less than about 0.050%, less than about 0.040%, less than about 0.035%, less than about 0.030%, less than about 0.025%, less than about 0.020%, less than about 0.015%, less than about 0.010%, less than about 0.009%, less than about 0.008%, less than about 0.007%, less than about 0.006%, less than about 0.005%, or less than about 0.001%, or less than about 0.0005%.
  • Each possibility is a separate embodiment.
  • At least a portion of the cannflavin in the cannabis composition comprises extracted, isolated, purified, and/or synthetic cannflavin.
  • a standardized cannabis extract comprising extracts from a natural source and isolated and/or synthetic cannflavin; wherein the extract comprises cannflavin at a predetermined minimal amount/concentration of at least 40ug per daily dose.
  • a standardized cannabis extract comprising extracts from a natural source and a predetermined minimal amount/concentration of at least 40ug per daily dose of isolated and/or synthetic cannflavin.
  • the standardized cannabis extract comprises a predetermined minimal amount of at least 60ug, per daily dose.
  • the disclosed cannabis composition can be further characterized by a minimal ratio (%) of cannflavin and THC concentrations (cannflavin/THC ratio (%)).
  • the cannflavin and THC concentrations are characterized by a ratio of at least about 0.070%.
  • the cannflavin and THC concentrations are characterized by a ratio of at least about 0.06%, at least about 0.07%, at least about 0.08%, at least about 0.085%, at least about 0.09%, at least about 0.10%, at least about 0.11%, at least about 0.12%, at least about 0.15%, at least about 0.20%, at least about 0.25%, at least about 0.30%, at least about 0.35%, at least about 0.45%, at least about 0.50%, at least about 0.60%, at least about 0.70%, at least about 0.90%, at least about 1.00%, at least about 5.00%, at least about 10.00%, at least about 25.00%, at least about 50.00%, at least about 75.00%, or more.
  • Each possibility is a separate embodiment.
  • the cannflavin and THC concentrations are characterized by a ratio of between about 0.06% and about 1000.00%, a ratio of between about 0.06% and about 500.00%, a ratio of between about 0.06% and about 100.00%, a ratio of between about 0.06% and about 25.00%, between about 0.06% and about 10.00%, between about 0.06% and about 5.00%, or between about 0.06% and about 1.00%, between about 0.06% and about 0.50%, or between about 0.06% and about 0.20%.
  • a ratio of between about 0.06% and about 1000.00% a ratio of between about 0.06% and about 500.00%, a ratio of between about 0.06% and about 100.00%, a ratio of between about 0.06% and about 25.00%, between about 0.06% and about 10.00%, between about 0.06% and about 5.00%, or between about 0.06% and about 1.00%, between about 0.06% and about 0.50%, or between about 0.06% and about 0.20%.
  • Each possibility
  • the disclosed cannabis composition may be further characterized by a minimal ratio (%) of cannflavin and CBD concentrations (cannflavin/CBD ratio (%)).
  • the cannflavin and CBD concentrations are characterized by a ratio of at least 27%. In some embodiments, the cannflavin and CBD concentrations are characterized by a ratio of at least 29%, at least 31%, at least 32%.
  • the cannflavin and CBD concentrations are characterized by a ratio of at least about 0.20%, at least about 1.00%, at least about 5.00%, at least about 7.50%, at least about 10.0%, at least about 25.0%, at least about 30.0%, at least about 50.0%, at least about 75.0%, at least about 100%, at least about 250%, at least 500%, at least about 750%, or at least about 1000%, or more.
  • the cannflavin and CBD concentrations are characterized by a ratio of between about 0.20% and about 2000.0%, a ratio of between about 1.0% and about 2000.0%, a ratio of between about 10% and about 2000.0%, between about 1.0% and about 500.00%, or between about 1.0% and about 100%.
  • a ratio of between about 0.20% and about 2000.0% a ratio of between about 1.0% and about 2000.0%, a ratio of between about 10% and about 2000.0%, between about 1.0% and about 500.00%, or between about 1.0% and about 100%.
  • the cannabis composition or the standardized extract comprises cannflavin at least at its minimal predetermined amount/concentration and additionally CBN at minimal concentration of at least 825 pg per daily dose.
  • the cannabis composition further comprises CBN at minimal concentrations of at least 825pg/day. According to some embodiments, the cannabis composition further comprises CBN at concentrations of at least 1075pg/day.
  • the cannabis composition further comprises CBN at a minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose or more.
  • CBN at a minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose or more.
  • the cannabis composition further comprises CBN at a maximal concentration of about 600,000ug per daily dose.
  • the cannabis composition further comprises CBN at an amount between any one of the minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose and a maximal concentration of about 600,000ug per daily dose.
  • CBN at an amount between any one of the minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose and a maximal concentration of about 600,000ug per daily dose.
  • Each possibility is a separate embodiment.
  • the minimal amount of CBN includes any dose of CBN (ug/day) determined based on, and corresponding to: at least the 50% percentile, at least the 55% percentile, at least the 60% percentile, at least the 65% percentile, at least the 70% percentile, at least the 75% percentile, at least the 80% percentile, at least the 85% percentile, at least the 90% percentile, at least the 95% percentile, at least the 99% percentile, at least the 100% percentile, or more.
  • CBN ug/day
  • the cannabis composition further comprises CBN at an amount of at least about 825ug/day for use in treating one or more condition and/or symptom, including sleep disorder, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • condition and/or symptom including sleep disorder, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • the cannabis composition further comprises CBN at an amount of at least about 825ug/day for use in treating pain.
  • the pain includes, but is not limited to, chronic and/or acute pain of one or more of: orthopedic pain, muscles pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof.
  • orthopedic pain muscles pain
  • spinal disc herniation pain neuropathic pain
  • widespread pain abdominal pain, and/or headaches, or any combination thereof.
  • headaches or any combination thereof.
  • CBN is added to the cannabis composition or the standardized extract.
  • CBN is added to the cannabis composition or the standardized extract at a minimal amount of at least 825ug/day or at least 1075ug/day.
  • CBN is added to the cannabis composition or the standardized extract when CBN amounts are below a minimal concentration of at least 825ug/day.
  • e composition comprises extracted, isolated, purified, and/or synthetic CBN, or any combination thereof. Each possibility is a separate embodiment.
  • At least a portion of the CBN added to the composition comprises isolated and/or synthetic CBN.
  • isolated and/or synthetic CBN are separate embodiments.
  • the standardized cannabis extract comprises at least about 2.6% (w/w) THC, at least about 2.6% (w/w) CBD, at least about 0.005% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • the standardized cannabis extract comprises at least about 5.2% (w/w) THC, at least about 5.2% (w/w) CBD, at least about 0.01% (w/w) cannflavin and optionally 0.5% (w/w) Vitamin E.
  • the standardized cannabis extract comprises THC and/or CBD concentrations of at least about 2.5% (w/w), at least about 5.0% (w/w), at least about 7.5% (w/w), at least about 10% (w/w), at least about 12.5% (w/w), at least about 15% (w/w), at least about 17.5% (w/w), at least about 20% (w/w), at least about 25% (w/w), at least about 30% (w/w), or at least about 35% (w/w), or at least about 40% (w/w), or any combination thereof.
  • THC and/or CBD concentrations of at least about 2.5% (w/w), at least about 5.0% (w/w), at least about 7.5% (w/w), at least about 10% (w/w), at least about 12.5% (w/w), at least about 15% (w/w), at least about 17.5% (w/w), at least about 20% (w/w), at least about 25% (w/w), at least about 30% (w/w), or at least about 35% (w/w), or
  • the standardized cannabis extract comprises THC and/or CBD concentrations of between about 2.5% (w/w) and about 50% (w/w), between about 5.0% (w/w) and about 40% (w/w), between about 7.5% (w/w) and about 35% (w/w), between about 10% (w/w) and about 30% (w/w), or between about 15% (w/w) and about 25% (w/w), or any combination thereof.
  • THC and/or CBD concentrations of between about 2.5% (w/w) and about 50% (w/w), between about 5.0% (w/w) and about 40% (w/w), between about 7.5% (w/w) and about 35% (w/w), between about 10% (w/w) and about 30% (w/w), or between about 15% (w/w) and about 25% (w/w), or any combination thereof.
  • THC and/or CBD concentrations of between about 2.5% (w/w) and about 50% (w/w), between about 5.0% (w/w) and about 40% (w/w), between about 7.
  • the cannabis extract is enriched with cannflavin; and wherein the cannabis extract enriched with cannflavin comprises at least about 2 times the predetermined minimal amount/concentration of cannflavin.
  • the standardized cannabis extract includes cannflavin at an amount between the predetermined minimal amount and a maximum amount of about 500,000ug, per daily dose.
  • the standardized cannabis extract comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug, per daily dose.
  • the standardized cannabis extract comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug per daily dose, about 400,000ug per daily dose, about 350,000ug per daily dose, about 300,000ug per daily dose, about 250,000ug per daily dose, about 200,000ug per daily dose, about 150,000ug per daily dose, about 100,000ug per daily dose, about 80,000ug per daily dose, about 60,000ug per daily dose, about 40,000ug per daily dose, about 20,000ug per daily dose, or about 10,000ug per daily dose.
  • 500,000ug per daily dose about 400,000ug per daily dose, about 350,000ug per daily dose, about 300,000ug per daily dose, about 250,000ug per daily dose, about 200,000ug per daily dose, about 150,000ug per daily dose, about 100,000ug per daily dose, about 80,000ug per daily dose, about 60,000ug per daily dose, about 40,000ug per daily dose, about 20,000ug
  • the standardized cannabis extract comprises cannflavin at maximal amount/concentration of less than 5.0000%.
  • the standardized cannabis extract comprises cannflavin at maximal amount/concentration of less than 5.0000%, less than 4.0000%, less than 3.0000%, less than 2.0000%, less than 1.0000%, less than 0.9000%, less than 0.8000%, less than 0.7000%, less than 0.6000%, less than 0.5000%, less than 0.4000%, less than 0.3000%, less than 0.2000%, less than 0.1000%.
  • cannflavin at maximal amount/concentration of less than 5.0000%, less than 4.0000%, less than 3.0000%, less than 2.0000%, less than 1.0000%, less than 0.9000%, less than 0.8000%, less than 0.7000%, less than 0.6000%, less than 0.5000%, less than 0.4000%, less than 0.3000%, less than 0.2000%, less than 0.1000%.
  • the maximal concentration of cannflavin in the standardized cannabis extract is less than about 0.099%, less than about 0.095%, less than about 0.094%, less than about 0.093%, less than about 0.092%, less than about 0.091%, less than about 0.090%, less than about 0.080%, less than about 0.070%, less than about 0.060%, less than about 0.050%, less than about 0.040%, less than about 0.035%, less than about 0.030%, less than about 0.025%, less than about 0.020%, less than about 0.015%, less than about 0.010%, less than about 0.009%, less than about 0.008%, less than about 0.007%, less than about 0.006%, less than about 0.005%, or less than about 0.001%, or less than about 0.0005%.
  • Each possibility is a separate embodiment.
  • the maximal concentration of cannflavin in the standardized cannabis extract is between about 5.0000% and about 0.00001%, between about 5.0000% and about 0.5000%, between about 0.099% and about 0.00001%.
  • each possibility is a separate embodiment.
  • the maximal concentration of cannflavin in the composition is between about 5.0000% and about 0.6000% between about 5.0000% and about 1.0000%, between about 3.0000% and about 1.0000%, or between about 2.0000% and about 0.6000%.
  • the maximal concentration of cannflavin in the composition is between about 0.095% and about 0.00001%, between about 0.095% and about 0.0001%, between about 0.095% and about 0.001%, or between about 0.095% and about 0.010%.
  • the maximal concentration of cannflavin in the composition is between about 0.095% and about 0.00001%, between about 0.095% and about 0.0001%, between about 0.095% and about 0.001%, or between about 0.095% and about 0.010%.
  • the cannflavin includes cannflavin A
  • a method for classifying cannabis compositions as being suitable for the treatment of one or more condition and/or symptom comprising: receiving a potential cannabis composition; evaluating the content of cannflavin in the potential cannabis composition; classifying the composition as being suitable for the treatment of the one or more condition and/or symptom when the cannflavin content is at or above a predetermined minimal amount/concentration; and wherein the one or more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof; wherein, in some embodiments, the predetermined minimal amount is at least 40ug, per daily dose. In some embodiments, the predetermined minimal amount is at least 60ug, per daily dose.
  • the method for classifying cannabis compositions further comprising labeling the potential composition as being suitable for the treatment of the one or more condition and/or symptom when the cannflavin content is at or above the predetermined minimal amount/concentration.
  • labeling the potential composition as being suitable for the treatment of the one or more condition and/or symptom includes labeling the composition as being suitable for the treatment of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof.
  • labeling the composition as being suitable for the treatment of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof includes labeling the composition as being suitable for the treatment of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof.
  • labeling the potential composition as being suitable for the treatment of sleep difficulties includes labeling the composition as being suitable for the treatment of sleep disorder including Insomnia.
  • labeling the potential composition as being suitable for the treatment of the sleep difficulties includes labeling the composition as being suitable for the treatment of sleep disorder including Insomnia and/or circadian rhythms sleep-wake phase disorder (SWPD).
  • sleep disorder including Insomnia and/or circadian rhythms sleep-wake phase disorder (SWPD).
  • SWPD circadian rhythms sleep-wake phase disorder
  • the sleep disorder includes insomnia.
  • sleep difficulties include insomnia.
  • labeling the potential composition as being suitable for the treatment of pain includes labeling the composition as being suitable for the treatment of chronic pain and/or acute pain.
  • labeling the potential composition as being suitable for the treatment of pain includes labeling the composition as being suitable for the treatment of one or more of orthopedic pain, muscles pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof.
  • the method for classifying cannabis compositions further comprising labeling the potential composition as being suitable for the treatment of the one or more condition and/or symptom when the cannflavin content is at or above the predetermined minimal amount/concentration; and when the cannflavin and THC concentrations are characterized by a cannflavin to THC ratio of at least about 0.07% and/or the CBN concentration is at or above a minimal amount/concentration of 825ug per daily dose.
  • the cannabis composition further comprises CBN at a minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose or more.
  • CBN at a minimal concentration of at least about 800pg per daily dose, at least about lOOOug per daily dose, at least about 2000ug per daily dose, at least about 5000ug per daily dose, at least about 10,000ug per daily dose, at least about 25,000ug per daily dose, at least about 100,000ug per daily dose, ,at least about 500,000ug per daily dose or more.
  • the cannflavin includes cannflavin A.
  • a method for classifying cannabis compositions as being suitable for the treatment of one or more condition and/or symptom comprising: receiving a potential cannabis composition; evaluating the level of cannflavin in the potential cannabis composition; classifying the composition as being suitable for the treatment of the one or more condition and/or symptom when the amount/concentration of cannflavin is equal to or above a predetermined amount; and wherein the one or more condition and/or symptom is selected from sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof.
  • the method further comprises labeling the potential composition as being suitable for the treatment of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof when the concentration of cannflavin is equal to or above the predetermined amount.
  • the method further comprising labeling the potential composition as being suitable for the treatment of sleep difficulties, pain, headaches, abdominal pain and anxiety, or any combination thereof when the predetermined minimal amount is at least 40ug, per daily dose, at least about 50ug, at least about 60ug, at least about 70ug, at least about 80ug, or at least about 90ug.
  • the predetermined minimal amount is at least 40ug, per daily dose, at least about 50ug, at least about 60ug, at least about 70ug, at least about 80ug, or at least about 90ug.
  • labeling the potential composition as being suitable for the treatment of sleep difficulties includes labeling the composition as being suitable for the treatment of Insomnia. In some embodiments, labeling the potential composition as being suitable for the treatment of sleep difficulties includes labeling the composition as being suitable for the treatment of a sleep disorder.
  • the selection comprises choosing according to a product specification which outlines the concentration of the cannabinoids found in the composition. According to some embodiments, the selection comprises choosing according to a measurement/analysis of a cannabis composition/extract. According to some embodiments, the selection comprises measuring the amount/concentration of the cannabinoid, for example by HPLC.
  • the composition is selected based on an analysis of the content of cannflavin in the plurality of cannabis compositions. According to some embodiments, based on the analysis of the content cannflavin is added to the composition to reach the predetermined minimal content, or above. According to some embodiments cannflavin is added to the composition if the content of cannflavin measured is below a predetermined minimal amount/concentration.
  • the potential composition is classified as being suitable for the treatment of sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof, if the concentration of cannflavin is at least about 40 ug per daily dose, at least about 50 ug per daily dose, at least about 60 ug per daily dose, at least about 70 ug per daily dose, at least about 80 ug per daily dose, at least about 90 ug per daily dose, or at least about 100 ug per daily dose.
  • cannflavin is added to the composition if the content of cannflavin is below 40 ug per daily dose.
  • cannflavin is added to the composition if the content of cannflavin is below 50 ug per daily dose. According to some embodiments cannflavin is added to the composition if the content of cannflavin is below 60 ug per daily dose. According to some embodiments cannflavin is added to the composition if the content of cannflavin is below 70 ug per daily dose. According to some embodiments cannflavin is added to the composition if the content of cannflavin is below 80 ug per daily dose. According to some embodiments cannflavin is added to the composition if the content of cannflavin is below 90 ug per daily dose. According to some embodiments cannflavin is added to the composition if the content of cannflavin is below 100 ug per daily dose.
  • cannflavin is added to the composition if the content of cannflavin measured is below 0.012 % w/w. According to some embodiments cannflavin is added to the composition if the content of cannflavin measured is below 0.018%.
  • the suitable cannabis composition comprises a content of cannflavin between the predetermined minimal amount/concentration and a maximum amount/concentration of about 500,000ug, per daily dose.
  • the suitable cannabis composition is enriched with cannflavin content.
  • the cannabis composition is a suitable cannabis composition; in some embodiments, a suitable cannabis composition comprises a standardized extract; in some embodiments, the suitable cannabis composition comprises a predetermined minimal amount/concentration per day of cannflavin; in some embodiments, the suitable cannabis composition comprises a predetermined minimal amount/concentration per day of at least 40ug cannflavin; in some embodiments, the suitable cannabis composition comprises a predetermined minimal amount/concentration per day of at least 60ug cannflavin.
  • the cannabis composition comprises a standardized extract.
  • a potential/suitable/optional cannabis composition comprises a standardized extract.
  • a method for treating one or more condition and/or symptom in a subject in need thereof comprising: administering to the subject a therapeutically effective amount of a cannabis composition comprising a cannflavin at amount/concentration of at least 40ug per daily dose, and wherein the condition and/or symptom includes one or more of sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • a method for treating one or more condition and/or symptom in a subject in need thereof comprising: administering to the subject a therapeutically effective amount of a cannabis composition comprising a cannflavin at amount/concentration of at least 40ug per daily dose, and wherein the condition and/or symptom includes one or more of sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • Each possibility is a separate embodiment.
  • a method for treating one or more condition and/or symptom in a subject in need thereof comprising: administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin, and wherein the condition and/or symptom includes one or more of sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin
  • the condition and/or symptom includes one or more of sleep difficulties, pain, headaches, abdominal pain, and anxiety, or any combination thereof.
  • the predetermined minimal amount is at least 60 ug cannflavin, per daily dose.
  • a method for treating sleep difficulties in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin.
  • sleep difficulties include sleep disorder.
  • sleep difficulties comprise one or more of: difficulty in falling asleep, difficulty in maintaining continuous sleep, having low-quality sleep ‘light sleep’, fragmented/impaired sleep, and insufficient sleep, or any combination thereof.
  • sleep difficulties comprise sleep disorders including Insomnia. In some embodiments, sleep difficulties comprise sleep disorders including circadian rhythms sleep-wake phase disorder (SWPD).
  • SWPD sleep-wake phase disorder
  • circadian rhythms sleep-wake phase disorder includes advanced phase (ASWPD) and/or delayed phase (DSWPD).
  • ASWPD advanced phase
  • DSWPD delayed phase
  • a method for treating pain in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin.
  • the pain comprises one or more of orthopedic pain, muscle pain, spinal disc herniation pain, neuropathic pain, widespread pain, abdominal pain, and/or headaches, or any combination thereof.
  • a method for treating abdominal pain in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin.
  • a method for treating abdominal headaches in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin.
  • a method for treating abdominal anxiety in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a cannabis composition comprising a predetermined minimal amount/concentration of 40ug per daily dose cannflavin.
  • At least one condition and/or symptom comprises a comorbidity associated with at least one additional medical condition; and wherein in some embodiments the at least one additional medical condition includes Post-Traumatic Stress Disorder (PTSD), fibromyalgia (FM), Inflammatory Bowel Disease (IBD), cancer, pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • Post-Traumatic Stress Disorder PTSD
  • FM fibromyalgia
  • IBD Inflammatory Bowel Disease
  • cancer pain, diabetes, head injury, and epilepsy, or any combination thereof.
  • a condition and/or symptom of the present invention may be characterized by, and may include one or more “parameter” - a term used herein to include, but is not limited to, duration (i.e., transient, acute or chronic) and severity (i.e., frequency and intensity) related to condition and/or symptom, as experienced or estimated, and self-reported by the subject, or as estimated or measured clinically, by means accepted in the art.
  • a condition and/or symptom of the present invention may be characterized by at least one parameter including transient, acute, chronic, severity, frequency, intensity, or any combination thereof.
  • improvement refers to alleviation or amelioration of the condition and/or symptom in at least one parameter characterizing a specific condition and/or symptom, compared between before and after receiving treatment with the herein disclosed cannabis composition, and as experienced or estimated, and self-reported by the subject, or as estimated or measured in the clinic by means accepted.
  • sleep difficulties/problems/disturbance include, but is not limited, for example to: subject’s complaints of sleeping difficulties including difficulty in falling asleep (i.e., initiating sleep), difficulty in maintaining sleep (i.e., trouble sleeping, staying asleep/continuous sleep), experiencing impaired sleep, fragmented or interrupted sleep, poor sleep, having low-quality sleep (i.e., not a good sleep), insufficient sleep, ‘light sleep’, experiencing excessive sleepiness, having movements of legs or limbs during sleep, abnormal muscle tonus (i.e., contraction) during sleep, disordered/abnormal breathing/respiration during sleep, and/or snoring, or any combination thereof.
  • subject s complaints of sleeping difficulties including difficulty in falling asleep (i.e., initiating sleep), difficulty in maintaining sleep (i.e., trouble sleeping, staying asleep/continuous sleep), experiencing impaired sleep, fragmented or interrupted sleep, poor sleep, having low-quality sleep (i.e., not a good sleep), insufficient sleep, ‘light sleep’, experiencing excessive sleepiness, having movements
  • a condition and/or symptom may be manifested as “primary” which means it is a distinct diagnostic entity that may arise spontaneously for unknown or obscure reasons (i.e., idiopathic) and is unrelated to a possible co-occurrence (comorbidity) of another medical/psychiatric/neurologic condition the suffering subject may have simultaneously; or a condition and/or symptom may be manifested as “secondary”, if it is related by causality or otherwise correlated with at least one other medical/psychiatric/neurologic condition the suffering subject have. Both primary and secondary can comorbidities.
  • Example 6 The study described in Examples 1-6 was approved by the Ethics Committee of Shaare- Zedek Medical Center, Jerusalem, Israel. (Helsinki reference number 0340-21-SZMC which is related to a 1 st clinical and chemical data set providing the basis for Example 1 describing sleeping difficulties; and Helsinki reference number 00245-21-SZMC which is related a 2 nd clinical and chemical data set providing the basis for Examples 2-5 describing pain, headaches, abdominal pain, and anxiety, respectively, as well as to Example 6.
  • Clinical data was collected by phone interviews.
  • Patients were eligible to participate in the study if they were Hebrew speaking and aged above 18 years old.
  • the patients answered a questionnaire regarding the perceived efficacy of the cannabis treatment in reducing the level of their condition and/or symptom on a scale of 1- 10 or 1-7 as indicated hereinbelow in the specific examples, where 1 represents lack of any cannabis effect (i.e., inefficient/ineffective treatment) and 10 or 7, represents high efficacy of treatment (i.e., extremely effective).
  • the strains indicated by patients in the questionaries were collected from various approved cultivators in Israel and analyzed for chemical data analysis of the phytocannabinoid cannabis molecule content in each strain by a high-performance liquid chromatography (HPLC) with an Ultraviolet-visible photodiode array (PDA) detector.
  • HPLC high-performance liquid chromatography
  • PDA Ultraviolet-visible photodiode array
  • the chemical analyzes were performed on fresh and unopened samples of inflorescence strains from Panaxia’s pharmacy warehouse rather than from samples obtained from the patients.
  • Example 1 using an automated clustering algorithm augmented with manual refinement by analytical chemists, 59 mutually exclusive cannabis molecules were identified, by both their relative (to THC) retention times (RRT) and PDA spectra. Nineteen (19) of these were cannabinoids whose identity, RRT and spectrum were already familiar to the inventors, whereas the other forty (40) were unknown. In Examples 2-6, chemical and statistical analyses included only those 19 “known” cannabis molecules.
  • Example 1 when applied on the 1 st clinical and chemical data set (Helsinki reference number 0340-2I-SZMC), the above-described approach identified cannflavin A as the molecule most positively correlated, and in a statistically significant manner, with treatment efficacy in medical cannabis consumers having symptoms of sleeping difficulties including insomnia including difficulty waking up, falling asleep or maintaining sleep, and participated in the study.
  • the flavonoid Cannflavin A was identified as Cannflavin A based on the following:
  • the peaks comprising this cluster have a RRT range of 0.57-0.60 whereas the RRT of the cannflavin A standard (provided by Cayman Chemical, item no. 21970, batch no. 0638046) is 0.60 (cannflavin A RT is 8.227, THC RT is 13.610) in the specific HPLC method applied in this study and is shown in FIG. 1 demonstrating a retention time identity and growth in Cannflavin A area in the spiked sample in direct proportion to the amount of standard added. 2.
  • the UV spectra of these peaks match the spectrum of the cannflavin A standard (compare FIG. 2A with FIG. 2B).
  • treatment efficacies of most of the indications and/or symptoms tested for were not found to be positively correlated in a statistically significant manner with cannflavin A concentration, these include: cognitive impairment, inability to concentrate, depression, lack of appetite, nausea, and muscle stiffness, as presented in Table 2 below.
  • the data was aimed to decrease this effect by normalizing the concentrations of the studied cannabis molecules in each batch/strain to the total THC amounts of the batch/strain. This was done to achieve a more accurate representation of the amount of each molecule consumed by patients.
  • the concentration of each molecule of each batch was divided by its total THC amount.
  • Total THC amount was calculated, per batch, as THC amount + 0.877 x THCA amount (accounting to full decarboxylation of THCA to THC, as expected in consumption via smoking).
  • the total THC value of each cluster (representing a cannabis molecule) for each of the strains was calculated as the median of the strain’s batches.
  • a minimal dose of 39.9 ug/day (rounded to 40ug/day) of cannflavin A was determined based on the 50% percentile, which corresponds to 0.012% (w/w), and considering minimal consumption of at least about 0.333 grams of cannabis per day by a subject (i.e., 1.2 miligrams of cannflavin A per month); and a minimal amount/concentration of 59ug/day (rounded to 60 ug/day) of cannflavin A was determined based on the 75% percentile, which corresponds to 0.018% (w/w), and considering minimal consumption of at least about 0.333 grams of cannabis per day by a subject (i.e., 1.8 miligrams of cannflavin A per month).
  • the median of the ratio of the concentrations of cannflavin A and total THC (cannflavin A to Total THC ratio) and that of cannflavin A and total CBD across the strains was calculated and considered as the minimum ratio required for efficacious treatment of the condition and/or symptom.
  • the surprising findings disclosed herein which are the result of a comprehensive clinical and chemical analyses performed on a wide range of data, allow choosing from a plurality of potential/optional compositions having a suitable amount/concentration of cannflavin of at least about 40ug per daily dose, as well as producing cannabis compositions including the same - that ensures a consistent therapeutic effect on patients, making it suitable for treatment of any one of sleeping difficulties, pain, headaches, abdominal pain, and/or anxiety, or any combination thereof.
  • Example 1 Efficacy evaluation of potential cannabis compositions in treating sleeping difficulties, and identification of cannflavin A as a cannabis molecule whose concentration correlates with a positive outcome.
  • Table 3 Medical background of the 98 patients having sleep difficulties with level of severity ranked 4 and 5.
  • the questionnaires included demographic data, such as age, gender, employment status, and years of cannabis, as summarized in Table 4. Patients had a median age of 43.5y/o and 74 (76%) of them were males. During the study period, a majority of patients (56%) were employed, with 27 (28%) of the patients unemployed due to their illness. 44 (45%) of the patients reported that they had used medical cannabis treatment for over 3 years.
  • 12 strains of cannabis namely Persian Kush, Black label, Havarra wedding, Zarrdde gold, Jerusalem espress, De Dutch, Kush Ben Yamin, Super silver bullet, Red Rhino, Kahavvai mode, Tachlta Till, Argvana heart.
  • the patients answered a questionnaire regarding the perceived efficacy of the cannabis treatment in reducing the level of sleeping difficulties on a scale of 1-10, where 1 represents lack of any cannabis effect (i.e., inefficient/ineffective treatment) and 10 represents high efficacy of treatment (i.e., extremely effective).
  • the ranked efficacy scores, belonging to the 98 patients suffering from severe sleeping difficulties (ranked 4 or 5) was included in this study and was correlated with the chemical data.
  • the above comprises the clinical data.
  • Peaks of the resulting chromatograms are assumed to be cannabis molecules. Nineteen (19) of these peaks could be identified based on their UV spectra and relative (to THC) RT (RRT), and as compared with commercial analytical standards. Quantification of each of these cannabis molecules was also performed, using their predetermined relative response factors (RRF) to an ibuprofen external standard. All the other significant peaks, which could not be identified, were classified by their UV spectra and RRT, and their areas under the curve (corresponding to their concentration) were recorded.
  • RRF relative response factors
  • the RRT and spectra data for all observed molecules (peaks in the HPLC chromatograms) in all samples were subsequently analyzed by a K-means classification algorithm.
  • K-means classification algorithm For an initial clustering, a two-part K-means algorithm was applied for clustering molecules, characterized by their RRT, from all the HPLC runs of all the batches. This is an unsupervised machine learning algorithm, used for grouping data into clusters with similar characteristics.
  • Each peak in each HPLC run represents a different, unique molecule, and therefore a constrained version of the K-means algorithm was applied.
  • the constraints were set such that 19 known cannabis molecules will host unique clusters.
  • the number of clusters was automatically determined by Elbow and Silhouette techniques, and each cluster represented a different molecule.
  • This two-part algorithm was first run on the spectra data, grouping all peaks with similar spectra. Then a clustering based on RRT was applied, thus dividing all molecules into clusters using a two-dimensional method, based on both spectra and RRT.
  • clusters were further explored by plotting for each cluster an overlay of the spectra of all its peaks (from the different HPLC runs), allowing easy identification of outlier spectra which most probably belong to another cluster with a nearby RRT.
  • the clusters were refined manually by analytical chemists to ensure that each cluster indeed contained all the peaks, from all HPLC runs, and only these peaks, related to this cluster/molecule.
  • This approach classified 59 cannabis molecules.
  • the concentration of each molecule was evaluated according to the area under the curve value in each chromatogram standardized to the area of an ibuprofen standard injected in each HPLC run.
  • the concentration of each cluster (representing a cannabis molecule) for each of the 12 strains was calculated as the median of the strain’s batches.
  • absolute amounts were also calculated using their analytical standards.
  • the peaks comprising this cluster have a RRT range of 0.57-0.60 whereas the RRT of the cannflavin A standard (provided byCayman Chemical, item no. 21970, batch no. 0638046) is 0.60 (cannflavin RT is 8.227, THC RT is 13.610) in the specific HPLC method applied in this study and is shown in FIG. 1 demonstrating a retention time identity and growth in Cannflavin A area in the spiked sample in direct proportion to the amount of standard added 2.
  • the UV spectra of these peaks match the spectrum of the cannflavin A standard (compare FIG. 2A with FIG. 2B).
  • the complexity of researching cannabis treatment in Israel is due in part to the variety of available strains, THC and CBD levels for each strain, and a variety of consumption methods including smoking, vaping, and orally-used oil.
  • patients can consume more than one strain in the same month, with varying doses of each strain.
  • patients reported using 12 unique cannabis strains.
  • As patients self-titrate cannabis consumption to standardize THC intake the more THC in the strain, the less patients consume in individual sessions), this study aimed to decrease this effect by normalizing the concentrations of the studied cannabis molecules in each batch/strain to the total THC amounts of the batch/strain. This was done to achieve a more accurate representation of the amount of each molecule consumed by patients.
  • the concentration of each molecule of each batch was divided by its total THC amount.
  • Total THC amount was calculated, per batch, as THC amount + 0.877 x THC A amount (accounting to full decarboxylation of THC A to THC, as expected in consumption via smoking).
  • the total THC value of each cluster (representing a cannabis molecule) for each of the 12 strains was calculated as the median of the strain’s batches.
  • each cannabis strain was assigned a representative efficacy score, based on the mean efficacy assigned to the strain in the questionnaire. As the efficacy score was provided to a strain, regardless of batch, the chemical data for each strain was taken as the median for each peak (representing a cannabis molecule) across all batches of the strain.
  • a potential efficacious cannabis molecule’s concentration should be positively correlated with treatment efficacy (as reported by the patients), across all strains, in a statistically significant manner.
  • a molecule showing a statistically significant high correlation indicates that as its dosage increases the treatment of sleep difficulties/insomnia is more effective.
  • a Spearman correlation was then used to quantify the correlation between the questionnaire’s efficacy of each strain (the label) and the concentration (divided by the THC level) of a specific cannabis molecule in each strain (i.e., the clinical data vs. the chemical data of each of the 59 clusters). Since 59 clusters were tested, the p-values were adjusted using the False Discovery Rate (FDR) method, taking into account multiple tests.
  • FDR False Discovery Rate
  • the Spearman correlation coefficient (r) was 0.841 with a p-valuc of 0.0238 after multiple testing corrections using the FDR method, indicating a statistically significant positive correlation between cannflavin A concentration and treatment efficacy of severe sleeping difficulties, as can be seen in FIG. 3A.
  • a minimal daily dose of 40ug/day was determined based on the strains concentrations 50% percentile, which was 0.012%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 60ug/day was determined based on the 75% percentile which was 0.018% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • Cannflavin A to THC ratio (calculated as (% cannflavin / % THC) X 100%) and Cannflavin A to CBD ratio (calculated as (% cannflavin / % CBD) X 100%) was calculated based on their concentrations for each of the 12 strains.
  • the median of this ratio (0.12%) for THC and (29%) for CBD can be considered a minimum ratio of Cannflavin A to THC and CBD, respectively, needed for the efficacious treatment of sleep difficulties.
  • Example 2 Efficacy evaluation of potential cannabis compositions in the treatment of pain, and identification of cannflavin A as a cannabis molecule whose concentration correlates with a positive outcome
  • a potential efficacious cannabis molecule’s concentration should be positively correlated with treatment efficacy (as reported by the patients), across all strains, in a statistically significant manner.
  • treatment efficacy as reported by the patients
  • a molecule showing a statistically significant high correlation indicates that as its dosage increases the treatment of pain in a population of fibromyalgia patients is more effective.
  • a Spearman correlation was then used to quantify the correlation between the questionnaire’s efficacy scores of each strain (the label) and the concentration (divided by the THC level) of a specific cannabis molecule in each strain (i.e., the clinical data vs. the chemical data of each of the 19 clusters representing known cannabinoids, including cannflavin A). Since 19 clusters were tested, the p-values were adjusted using the False Discovery Rate (FDR) method, considering multiple tests.
  • FDR False Discovery Rate
  • a minimal daily dose of 40 ug/day was determined based on the strains concentrations 50% percentile, which was 0.012%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 60ug/day was determined based on the 75% percentile which was 0.018% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • Cannflavin A to THC ratio (calculated as (% cannflavin I % THC) X 100%) and Cannflavin A to CBD ratio (calculated as (% cannflavin I % CBD) X 100%) was calculated based on their concentrations for each of the 11 strains. The median of this ratio (0.078%, rounded to 0.080%) for THC and (32%) for CBD can be considered a minimum ratio of Cannflavin A to THC and CBD, respectively, needed for the efficacious treatment of pain.
  • THC and CBD were found to be significantly correlated with the effective treatment of pain.
  • Example 3 Efficacy evaluation of potential cannabis compositions in the treatment of headache, and identification of cannflavin A as a cannabis molecule whose concentration correlates with a positive outcome
  • a potential efficacious cannabis molecule’s concentration should be positively correlated with treatment efficacy (as reported by the patients), across all strains, in a statistically significant manner.
  • a molecule showing a statistically significant high correlation indicates that as its dosage increases the treatment of headaches is more effective.
  • a Spearman correlation was then used to quantify the correlation between the questionnaire’s efficacy of each strain (the label) and the concentration (divided by the THC level) of a specific cannabis molecule in each strain (i.e., the clinical data vs. the chemical data of each of the 19 clusters representing known cannabinoids, including cannflavin A). Since 19 clusters were tested, the -valucs were adjusted using the False Discovery Rate (FDR) method, taking into account multiple tests.
  • FDR False Discovery Rate
  • a minimal daily dose of 40 ug/day was determined based on the strains concentrations 50% percentile, which was 0.012%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 60ug/day was determined based on the 75% percentile which was 0.018% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • Cannflavin A to THC ratio (calculated as (% cannflavin / % THC) X 100%) and Cannflavin A to CBD ratio (calculated as (% cannflavin / % CBD) X 100%) was calculated based on their concentrations for each of the 7 strains. The median of this ratio (0.071%, rounded to 0.070%) for THC and (32%) for CBD can be considered a minimum ratio of Cannflavin A to THC needed for the efficacious treatment of headaches.
  • THC and CBD were found to be significantly correlated with the effective treatment of headaches.
  • Example 4 Efficacy evaluation of potential cannabis compositions in the treatment of abdominal pain, and identification of cannflavin A as a cannabis molecule whose concentration correlates with a positive outcome
  • a potential efficacious cannabis molecule’s concentration should be positively correlated with treatment efficacy (as reported by the patients), across all batches, in a statistically significant manner.
  • a molecule showing a statistically significant high correlation indicates that as its dosage increases the treatment of abdominal pain in a population of fibromyalgia or IBD patients is more effective.
  • a minimal daily dose of 40 ug/day was determined based on the strains concentrations 50% percentile, which was 0.012%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 60ug/day was determined based on the 75% percentile which was 0.018% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • Cannflavin A to THC ratio (calculated as (% cannflavin / % THC) X 100%) and Cannflavin A to CBD ratio (calculated as (% cannflavin I % CBD) X 100%) was calculated based on their concentrations for each of the 14 batches.
  • the median of this ratio (0.086%, rounded to 0.09%) for THC and (31%) for CBD can be considered a minimum ratio of Cannflavin A to THC and CBD, respectively, needed for the efficacious treatment of abdominal pain.
  • THC and CBD were found to be significantly correlated with the effective treatment of abdominal pain.
  • Example 5 Efficacy evaluation of potential cannabis compositions in the treatment of anxiety, and identification of cannflavin A as a cannabis molecule whose concentration correlates with a positive outcome
  • a potential efficacious cannabis molecule’s concentration should be positively correlated with treatment efficacy (as reported by the patients), across all strains, in a statistically significant manner.
  • treatment efficacy as reported by the patients
  • a molecule showing a statistically significant high correlation indicates that as its dosage increases the treatment of anxiety is more effective.
  • a Spearman correlation was then used to quantify the correlation between the questionnaire’s efficacy of each strain (the label) and the concentration (divided by the THC level) of a specific cannabis molecule in each strain (i.e., the clinical data vs. the chemical data of each of the 19 clusters representing known cannabinoids, including cannflavin A). Since 19 clusters were tested, the p-values were adjusted using the False Discovery Rate (FDR) method, taking into account multiple tests.
  • FDR False Discovery Rate
  • a minimal daily dose of 40 ug/day was determined based on the strains concentrations 50% percentile, which was 0.012%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 60ug/day was determined based on the 75% percentile which was 0.018% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • Cannflavin A to THC ratio (calculated as (% cannflavin / % THC) X 100%) and Cannflavin A to CBD ratio (calculated as (% cannflavin I % CBD) X 100%) was calculated based on their concentrations for each of the 8 strains. The median of this ratio (0.071%, rounded to 0.070%) for THC and (27%) for CBD (calculated in Example 6) can be considered a minimum ratio of Cannflavin A to THC and CBD, respectively, needed for the efficacious treatment of headaches.
  • Example 6 Efficacy evaluation of potential cannabis compositions in the treatment of pain, and identification of both cannflavin A and CBN as cannabis molecules whose concentrations correlate with a positive outcome
  • a potential efficacious combination of cannabis molecules concentrations should be positively correlated with treatment efficacy (as reported by the patients), across all strains, in a statistically significant manner.
  • treatment efficacy as reported by the patients
  • a combination of molecules showing a statistically significant high correlation indicates that as their dosages increase the treatment of pain is more effective.
  • a minimal daily dose of 825 ug/day was determined based on the strains concentrations 50% percentile, which was 0.248%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 1075ug/day was determined based on the 75% percentile which was 0.323% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • a minimal daily dose of 40 ug/day was determined based on the strains concentrations 50% percentile, which was 0.012%, and considering minimal daily consumption of at least about 0.333 grams of cannabis inflorescence by a subject (i.e., 10g per month); and a minimal daily dose of 60ug/day was determined based on the 75% percentile which was 0.018% and considering minimal daily consumption of at least about 0.333 grams by a subject (i.e., 10g per month).
  • Cannflavin A to THC ratio and total CBN to THC ratio were calculated for each of the 13 strains.
  • the medians of these ratios (0.07% and 1.3%, respectively) can be considered as minimum ratios of cannflavin A and CBN, respectively, to THC needed for the efficacious treatment of pain.
  • Cannflavin A to CBD ratio and total CBN to CBD ratio were calculated for each of the 13 strains.
  • the medians of these ratios (27% and 414%, respectively) can be considered as minimum ratios of cannflavin A and CBN, respectively, to CBD needed for the efficacious treatment of pain.
  • THC A or CBDA acid forms
  • Example 7 Clinical trial for evaluation of novel standardized cannabis extract formulations for the treatment of pain in fibromyalgia (FM) patients, including evaluation of treatment of anxiety and sleep difficulties.
  • FM fibromyalgia
  • Additional aim - the design of the herein described clinical data includes monitoring a therapeutic effect on anxiety and sleep difficulties in fibromyalgia patients suffering from pain and having comorbid anxiety and sleep difficulties, using the experimental results including the above-mentioned questionnaires (Pittsburgh Sleep Quality Index (PSQI) and Hospital anxiety and depression scale (HADS), and therefore the design further allows to evaluate the efficacy of the investigational product containing at least predetermined minimal amount/concentration of cannflavin A, compared to control, for treatment of anxiety and sleep difficulties.
  • PSQI Streus Sleep Quality Index
  • HADS Hospital anxiety and depression scale
  • Example of formulation 1 Standardized extract of 26mg/g (25mg/mL) THC, 26mg/g (25mg/mL) CBD, 0.05 mg/g Cannflavin A.
  • THC rich extract as a source of both THC and Cannflavin A
  • CBD rich extract as a main source of CBD
  • 360g of extract A is mixed with 398g of extract B, 9192g of MCT oil and 50g of Vitamin E.
  • the resulting 10,000g standardized extract contains 26mg/g of THC, 26mg/g of CBD and 0.05 mg/g Cannflavin A.
  • Example of formulation 2 Standardized extract of 26mg/g (25mg/mL) THC, 26mg/g (25mg/mL) CBD, 0.05 mg/g Cannflavin A.
  • 1188g of extract A is mixed with 1313.4g of extract B, 30333.6g of MCT oil and 165g of Vitamin E.
  • the resulting 33,000g standardized extract contains 26mg/g of THC, 26mg/g of CBD and 0.05 mg/g Cannflavin A.
  • Example of formulation 3 Standardized extract of 52mg/g (50mg/mL) THC, 52mg/g (50mg/mL) CBD, 0.1 mg/g Cannflavin A.
  • 720g of extract A is mixed with 796g of extract B, 8434g of MCT oil and 50g of Vitamin E.
  • the resulting 10,000g standardized extract contains 52mg/g of THC, 52mg/g of CBD and 0.1 mg/g Cannflavin A.
  • Example of formulation 4 Standardized extract of 52mg/g (50mg/mL) THC, 52mg/g (50mg/mL) CBD, 0.1 mg/g Cannflavin A.
  • 1800g of extract A is mixed with 1990g of extract B, 21085g of MCT oil and 125g of Vitamin E.
  • the resulting 25,000g standardized extract contains 52mg/g of THC, 52mg/g of CBD and 0.1 mg/g Cannflavin A.
  • Non-limiting formulations 1-4 assumes consumption of at least 0.8g product per day (formulation 1-2) or at least 0.4g product per day (formulation 3-4), which includes cannflavin A consumption of at least the predetermined minimal amount/concentration of 40ug per daily dose.
  • nonlimiting formulations 1-4 also represent an enriched cannabis extract that includes at least twice the predetermined minimal amount/concentration of at least 40ug cannflavin A per daily dose (i.e., at least t 80ug cannflavin A per daily dose).
  • Non-limiting formulations 1-4 include Cannflavin A to THC ratio and Cannflavin A to CBD ratio of about 0.2% [calculated as: ((% cannflavin / % THC) X 100%) or ((% cannflavin / % CBD) X 100%)].
  • the cannflavin A to THC ratio represents a ratio well above the minimum Cannflavin A to THC ratio of about 0.07%, needed for efficacious treatment of any one of the conditions and/or symptoms treatable by cannabis composition comprising a predetermined minimal amount/concentration of at least 40ug cannflavin A.
  • Cannflavin A to THC ratio or Cannflavin A to CBD ratio in standardized extract/cannabis composition of the invention can in the range from about 0.07% up to 1000.00% for Cannflavin A to THC ratio or between 27%-500,000% Cannflavin for A to CBD ratio.
  • Non-limiting formulations 1-4 include THC and CBD concentration of about 2.6%- 5.2%w/w each, however, these should not limit the concentration of THC and CBD in standardized extract/cannabis composition of the invention which in some embodiments, can include 10%, 15%, 20% 25%, 30%, 35%, 40%, 45%, or 50%.
  • Non-limiting formulations 1-4 also include representation of concentrations in % (w/w), however these are not affected by the amount consumed, do not correlate directly to the predetermined minimal amount, and with respect to cannflavin the concentration, in some embodiments it may range between 0.00001% cannflavin A and up to a maximal concentration of 5.0000% in standardized extract/cannabis composition of the invention.
  • non-limiting formulations 1-4 represent compositions of standardized extract fulfilling at least one of any one of the requirements of a cannabis composition
  • a cannabis composition comprising (i) the predetermined minimal amount/concentration of at least 40ug cannflavin A per daily dose; (ii) Cannflavin A to THC and Cannflavin A to CBD concentrations at the minimal characteristic ratio of at least about (0.070%) and (27%), respectively, required for efficacious treatment of any one of the conditions and/or symptom of the present invention; (iii) enriched amount of cannflavin A of at least twice the predetermined minimal amount/concentration (i.e., at least 80ug per daily dose); and (iv) in some embodiments, it may include CBN at amount of at least 825ug per daily dose.

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Abstract

L'invention concerne des compositions de cannabis comprenant de la cannflavine à ou au-dessus d'une concentration minimale prédéterminée pour un effet thérapeutique cohérent, et des procédés d'utilisation de celles-ci, pour traiter des difficultés du sommeil, la douleur, les maux de tête, la douleur abdominale et l'anxiété.
PCT/IL2023/050899 2022-08-25 2023-08-24 Compositions de cannabis enrichies en cannflavine pour un effet thérapeutique cohérent sur diverses affections WO2024042526A1 (fr)

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WO2019056128A1 (fr) * 2017-09-25 2019-03-28 Canopy Health Innovations Compositions comprenant du cannabidiol, du tétrahydrocannabinol, des terpènes et des flavonoïdes et leur utilisation dans le traitement de l'insomnie
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Publication number Priority date Publication date Assignee Title
WO2019056128A1 (fr) * 2017-09-25 2019-03-28 Canopy Health Innovations Compositions comprenant du cannabidiol, du tétrahydrocannabinol, des terpènes et des flavonoïdes et leur utilisation dans le traitement de l'insomnie
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SCHMIDT ELENA: "Flavonoids Fridays: Everything You Need to Know about Cannflavin B Flavor, Fragrance, and Health Benefits", ACS LABORATORY, 7 December 2021 (2021-12-07), XP093143405, Retrieved from the Internet <URL:https://www.acslab.com/flavonoids/flavonoids-fridays-everything-you-need-to-know-about-cannflavin-b-flavor-fragrance-and-health-benefits> [retrieved on 20240320] *
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