WO2022018709A1 - Compositions et méthodes de traitement de psychoses et de troubles psychotiques - Google Patents

Compositions et méthodes de traitement de psychoses et de troubles psychotiques Download PDF

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WO2022018709A1
WO2022018709A1 PCT/IB2021/057019 IB2021057019W WO2022018709A1 WO 2022018709 A1 WO2022018709 A1 WO 2022018709A1 IB 2021057019 W IB2021057019 W IB 2021057019W WO 2022018709 A1 WO2022018709 A1 WO 2022018709A1
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composition
psychedelics
serotonergic
terpenes
extract
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PCT/IB2021/057019
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Stephen Barnhill
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Ai Pharmaceuticals Jamaica Limited
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    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/70—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mental therapies, e.g. psychological therapy or autogenous training
    • 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
    • A61K31/01—Hydrocarbons
    • A61K31/015—Hydrocarbons carbocyclic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/4045—Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/074—Ganoderma
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/10—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/70—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H70/00—ICT specially adapted for the handling or processing of medical references
    • G16H70/40—ICT specially adapted for the handling or processing of medical references relating to drugs, e.g. their side effects or intended usage
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A90/00—Technologies having an indirect contribution to adaptation to climate change
    • Y02A90/10—Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Definitions

  • compositions and methods useful in the treatment of psychotic disorders, depression, anxiety, and related psychological conditions, and for patients afflicted therewith More particularly this relates to nutraceutical and/or pharmaceutical compositions comprising serotonergic psychedelics, cannabinoids, terpenes, flavonoids, and/or other botanical extracts useful for treating such conditions.
  • endocannabinoid system can be affected by exogenous cannabinoids, including plant-based cannabinoids.
  • Cannabinoids such as delta-9- tetrahydrocannabinol (THC) and cannabidiol (CBD) are major cannabinoids from Cannabis spp. Cannabis spp. have also been used medicinally for centuries. Their therapeutic value is the subject of many current studies.
  • the available treatment cannot be consumed by or administered to all people needing treatment, and/or may not address a particular patient's problems. Moreover, the underlying illness is often refractory. [8] Similar concerns about available treatments, side effects, toxicity, and effectiveness exist for psychological conditions that involve abnormal anxiety or depression. The economic impact of these conditions is huge on both the personal level for those directly impacted and on the societal level.
  • compositions generally comprising combinations of serotonergic psychedelics, certain cannabinoids, terpenes, and at least one edible or medicinal mushrooms or an extract or component derived therefrom are particularly useful or effective for treating a range of psychological disorders, particularly those in which psychoses or psychotic events are involved.
  • the serotonergic psychedelics generally comprise tryptamine psychedelics or phenylethylamine psychedelics.
  • the cannabinoids can be derived from any Cannabis spp.
  • the mushroom or mushroom extract present in the compositions is from any edible or medicinal mushroom species (other than a mushroom species known to contain psychedelics (e.g. 'magic mushrooms')).
  • the compositions optionally include other nutraceutical or botanical compounds to provide additional functionality or support.
  • compositions comprising one or more serotonergic psychedelics, one or more cannabinoids, one or more terpenes, and at least one edible or medicinal mushroom has many benefits, and the compositions provide certain useful properties, such as effectiveness including over a long period of time, low toxicity, no serious side effects, and good tolerance on the part of a wide range of subjects.
  • the methods generally comprise a step of administering a therapeutic composition to the subject.
  • the compositions generally comprise one or more serotonergic psychedelics, one or more cannabinoids, one or more terpenes, and one or more edible or medical mushrooms or and extract, fraction, or isolate thereof.
  • the composition further comprises one or more optional ingredients comprising at least one flavonoid, S- adenosylmethionine, methylfolate, omega-3 fatty acids, or vitamin D or a compound providing a biologically-available form thereof.
  • the psychological disorder comprises a psychosis or psychotic events, or abnormal anxiety or depression.
  • the disclosure also provides a plurality of dosing regimens that utilize the compositions, with and without serotonergic psychedelics included, on various schedules as dictated by the physiological or psychological health of the subject.
  • methods for optimizing a composition for use in treatment of a subject suffering from a psychological disorder.
  • the methods employ the use of artificial intelligence algorithms, such as classification algorithms, regression algorithms, clustering algorithms, or a combination thereof.
  • the methods generally comprise:
  • the psychological disorder comprises a psychosis or psychotic events, or abnormal anxiety or depression
  • this disclosure provides methods for treating a psychological disorder in a patient in need thereof.
  • the methods generally comprise the step of administering a composition comprising at least one serotonergic psychedelic in combination with at least one cannabinoid and at least one terpene, and at least one edible or medicinal mushroom or extract thereof.
  • the at least one cannabinoid and at least one terpene can be administered separately from, sequentially to, or simultaneously with the serotonergic psychedelic and edible or medicinal mushroom.
  • the at least one edible or medicinal mushroom or extract thereof can also be administered separately from, sequentially to, or simultaneously with the serotonergic psychedelic and cannabinoid.
  • compositions and methods for treating psychological disorders that include psychoses, psychotic events, abnormal anxiety, or abnormal depression.
  • compositions provide the benefits of certain compounds, serotonergic psychedelics, used for centuries by indigenous peoples and religious practitioners for their ability to produce altered states of consciousness, with the positive benefits of another natural substance, cannabis, also used for centuries.
  • the compositions further utilize certain beneficial edible or medicinal mushrooms, and other nutraceutical or pharmaceutical compounds. Used properly, these compositions have little risk, few side effects, and are effective for producing measurable and lasting results in patients suffering from such psychological disorders.
  • anxiety and “stress” as used herein are related terms. Stress is an unavoidable part of life and includes internal and/or external stimuli (stressors) which can impact individuals positively or negatively. Positive stress generally requires that a positive stressor manifests moderately and for a limited period of time. Negative stress can become anxiety for example when high levels of stress, which are perceived to have negative consequences are experienced over a prolonged periods of time. Statistics suggest that 10 - 30% of primary care patients suffer from anxiety disorders. Women, particularly those between 40-55 years, are more likely to experience problematic anxiety.
  • a degree of anxiety is always present in everyday life and for most people most of the time, it does not interfere with the enjoyment or quality of life of the person or subject, and does not result in seeking or requiring medical or psychological help. Such anxiety is considered normal and may be associated with feelings of depression, frustration, anger, fear, or sadness.
  • abnormal anxiety is anxiety that is present in a subject to an extent where the subject seeks or requires medical or psychological help, is unable to perform the tasks of everyday life, or whose enjoyment of or quality of life is diminished because of the anxiety they are experiencing.
  • Abnormal anxiety can be determined by any qualified medical or psychological professional, by self-reporting, or by use of standardized assessments instruments, inventories, or scales.
  • “Abnormal anxiety” is not absolute, but rather, an amount that is 'abnormal' for a specific individual.
  • “Depression”, like 'anxiety' can be normal wherein it does not rise to the level of interfering with one's enjoyment or quality of life, and does not result in and "abnormal depression.
  • Types of disorders the compositions and methods disclosed here are useful for include, in addition to psychotic disorders, disorders that entail abnormal anxiety or depression such as major depressive disorders, post-traumatic stress disorder, addictions and substance abuse disorders (including alcoholism, opiate and other drug additions, behavioral addictions), end-of-life depression, and the like.
  • Serotonergic psychedelics as used herein mean any of the family of compounds that interact with serotonin pathways in the nervous system, particularly with the class of 5-HT receptors that recognize serotonin compounds, and which produce hallucinogenic effects in a subject.
  • Serotonergic psychedelics useful herein include both tryptamine derivative and analogues and phenylethylamine derivatives and analogues, with affinity or avidity for any of the 5-HT receptors.
  • Serotonergic psychedelics can be naturally occurring or synthetically produced.
  • Cannabis " or " Cannabis spp.” as used herein refers to any plant of the genus Cannabis, including plants that may be classified as Cannabis sativa, Cannabis indica, or Cannabis ruderalis. It is well-known that despite the foregoing list, some experts believe that there are only 2 species, and still others consider that there is only a single species (generally, C. sativa). Whatever nomenclature is used, for purposes of this disclosure, “ Cannabis " includes all possible members of the genus, without regard to the species to which they are assigned.
  • 'cannabinoids means any of a class of compounds that generally can interact with one or more cannabinoid receptors, including the receptors of the endocannabinoid system, in particular, CB1 and CB2.
  • Cannabinoids include e.g., phytocannabinoids and synthetic cannabinoids.
  • Phytocannabinoids are found in several plant species, especially Cannabis spp. Among the most prevalent and most studied cannabinoids are tetrahydrocannabinol (THC), and cannabidiol (CBD).
  • cannabinoids that have been identified in Cannabis within certain classes including the tetrahydrocannabinols, cannabidiols, cannabigerols, cannabinols, cannabichromenes, and cannabinodiol.
  • Other cannabinoids such as cannabicyclol, cannabieslsoin, cannabitriol are currently classed as 'miscellaneous' by some researchers.
  • THC is not only a major cannabinoid in Cannabis spp., it is generally the compound responsible for the psychoactive effects of consuming Cannabis.
  • compositions may be created with various ratios of cannabinoids, such as the ratio of CBD to THC or other ratios depending the specific person or the specific condition being treated.
  • terpenes means any of the organic compounds commonly known as terpenes or terpenoids. Terpenes are generally aromatic compounds classified as isoprene derivatives. Terpenes suitable for use herein include hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, sesquaterpenes, tetraterpenes, polyterpenes, and norisoprenoids.
  • Exemplary terpenes that are particularly useful herein include alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, and valencene.
  • the term "edible” does not mean merely capable of being eaten. In that overly broad sense, even poisonous or toxic mushrooms are 'edible' however lethal or sickening or the like. In contrast “edible mushrooms” is used herein in the sense of mushrooms that are used traditionally or in modern times as sources of food, nutrients, nutraceuticals, flavors, and the like. Edible mushrooms are not toxic or poisonous as consumed.
  • “Medicinal mushrooms” as used herein means any mushroom species that has been used traditionally or in modern times as a source of medicinal or therapeutic benefits, healing properties, or the like. [43] Generally, mushrooms are grouped together as 'edible or medicinal' as there may be many crossovers and it may be difficult to clearly distinguish between the two groups. Examples of edible and/or medicinal mushrooms useful herein include Reishi mushroom ( Ganoderma lucidum), Lion's Mane ( Hericium erinaceus), and Cordyceps. More generally edible and/or medicinal mushrooms of the genera Ganoderma, Hericium, or Cordyceps are all suitable for use herein.
  • Reishi mushrooms have been reported to calm the central nervous system and/or have neuroprotective effect, and stimulate the immune system. Reishi has been reported to have a beneficial effect on the adrenals, and to be anxiolytic, reducing anxiety and promoting sleep. Reishi has also been associated with improved memory, and sharpened concentration and focus. Lion's Mane reportedly calms mental activity and modulates certain neurotransmitters. Cordyceps has been reported to have adaptagenic properties and stimulate the adrenals glands and modulates the nervous system.
  • flavonoids includes any of the class of polyphenolic molecules containing 15 carbon atoms that are naturally produced in plants and are soluble in water. Also included herein as “flavonoids” are natural or synthetic derivative or analogs thereof that have biological activity. Llavonoids of use herein can generally be divided in to 6 groups of structurally-related compounds: chalcones, flavones, isoflavonoids, flavanones, anthoxanthins and anthocyanins. Also useful are flavanols and catechins, as well as glucosides or other derivatives or analogs of any of the foregoing. The flavonoids are found in most fruits and vegetables, particular colorful ones. They are also prevalent in legumes (including soybeans), grains, green and black teas, as well as red wine.
  • Llavonoids have numerous functions in plants, and act as important cell messengers. Various flavonoids are believed to provide healthful benefits and functions to humans such as anti-viral, anti-cancer, anti-inflammatory, antiallergic, and anti-oxidant properties. They may also be cardio-protective, cholesterol-lowering, and anti-atherosclerotic. Llavonoids from any source may be used herein. Llavonoids isolated from Cannabis, such as cannaflavins A, B, and or C, are of interest in certain applications, as are vitexin, isovitexin, apigenin, kaempferol, quercetin, orientin, and luteolin, as well as the catechins found in Cannabis. [47] As used herein, the singular form of a word includes the plural, and vice versa, unless the context clearly dictates otherwise. Thus, the references "a”,
  • compositions or "a serotonergic psychedelic” includes a plurality of such “compositions” or “serotonergic psychedelic.”
  • ranges are provided in shorthand, so as to avoid having to list and describe each and every value within the range. Any appropriate value within the range can be selected, where appropriate, as the upper value, lower value, or the terminus of the range.
  • APM "Apollon Medical” strain of C. sativa
  • CBD cannabidiol
  • CBG cannabigerol
  • DMT N,N-Dimethyltryptamine
  • ECS endocannabinoid system
  • 5-HT 5-hydroxytryptamine
  • KNN K Nearest Neighbor
  • OCD obsessive compulsive disorder
  • SVM Support Vector Machines
  • THC tetrahydrocannabinol
  • compositions comprising one or more serotonergic psychedelics are provided.
  • the compositions further comprise one or more cannabinoids, one or more terpenes, and one or more edible or medicinal mushrooms or an extract, fraction, or isolate thereof.
  • the serotonergic psychedelics useful herein include but are not limited to tryptamine psychedelics, phenylethylamine psychedelics, or any combination thereof.
  • Tryptamine psychedelics such as N,N-dimethyltryptamine (DMT) and psilocybin as both suitable for use, as are any serotonergic metabolites, derivatives, or analogs thereof.
  • Phenylethylamine psychedelics suitable for use herein include but are not limited to LSD, mescaline, 2c psychedelics, or DOI, or any serotonergic metabolites, derivatives, or analogs thereof.
  • R' is hydrogen, chlorine, methyl, or not present
  • R' and R" share CH, (CH 2 ) 3 , ( CH 2 ) 4 , ( CH 2 ) 5 , or (CH 2 ) 6 .
  • the serotonergic psychedelics used in the compositions are agonists of one or more 5-HT receptors, such as 5-HT 1A , 5-HT 2A , or 5-HT 2C receptors.
  • Hallucinogens may serve as therapeutic treatments severe psychiatric disorders such as psychoses, anxiety, addictions (e.g. alcoholism), OCD, and cluster headache.
  • severe psychiatric disorders such as psychoses, anxiety, addictions (e.g. alcoholism), OCD, and cluster headache.
  • addictions e.g. alcoholism
  • OCD oxygen-driven psychiatric disorders
  • the inventor has discovered that by providing serotonergic psychedelics with additional compounds such as cannabinoids, terpenes, mushroom extracts, and such, more benefits can be derived from the treatments with better outcomes and fewer side effects.
  • compositions comprise one or more serotonergic psychedelics and cannabinoids comprising one or more of cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), or tetrahydrocannabinol (THC).
  • CBD cannabidiol
  • CBN cannabinol
  • CBG cannabigerol
  • THC tetrahydrocannabinol
  • the cannabinoids are derived from hemp, or the THC content is removed from the cannabinoids such that THC is present in the composition at less than about 0.3 percent. In various embodiments, the THC content may be less than 0.2, or even less than 0.1% of the composition.
  • the ratio of cannabinoids is set in the compositions.
  • the ratio of CBD to THC ranges from about 1:5 to about 30:1 or more. In other embodiments the ration may range from about 1:2 to about 10:1. In still other embodiments, the ratio of CBD to THC may be about 1:1 to 5:1. In other cases, the ration of e.g. CBD to CBG or CBN may be set based on any of a variety of factors, including the health status of the subject being treated, the symptoms of the subject, the condition(s) being treated, and or one or more physiological or genetic criteria.
  • compositions may be provided in completely customized or personalized formulations for each person being treated - i.e. as personalized medicines.
  • the compositions may be adjusted based on initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), specific symptomology, or the like.
  • the formulation of the compositions may also be changed based on the results from an initial treatment, subsequent treatment, or based on subsequent tests.
  • the cannabinoids are derived from Cannabis spp. or an extract thereof.
  • Cannabis can generally be concentrated or extracted (e.g. via mechanical or chemical means) to obtain cannabinoids.
  • Mechanical means of extracting oils from plants, such as pressing, have been used for centuries, and may be suitable for use herein.
  • Extraction via chemical means includes extraction with various volatile solvents that range from hydrocarbon solvents such as butane, hexanes or propane, to supercritical fluids, alcohol, steam, or even water. Two very common methods are extraction with supercritical carbon dioxide, or ethanol, both of which are particularly useful herein.
  • cannabinoids present in an ethanolic extract or supercritical C02 extract of Cannabis sativa are preferred for use herein.
  • the extract comprises one or more of Ringo's Gift, Harle Tsu, ACDC, Charlotte's Web, The Gift, or Pineberry strains of Cannabis sativa.
  • Apollon Medical (“APM”), a proprietary strain commercially available from Apollon Formularies, is also useful herein.
  • the composition in various embodiments include terpenes comprising one or more monoterpenes, one or more sesquiterpenes, or a combination thereof.
  • the terpenes comprise one or more of alpha bisabolol, alpha pinene, beta caryophyllene, beta pinene, borneol, camphor, camphene, caryophyllene oxide, cineole, delta-3 carene, eucalyptol, farnesenes, farnesol, fenchol, fenchone, geraniol, guaiol, humulene, isopulegol, limonene, linalool, menthol, myrcene, nerol, nerolidol, ocimene, pinene, phytol, pulegone, terpinene, terpineol, terpinolene, or valencene.
  • the terpenes preferably comprise one or more of limonene, myrcene, beta-caryophyllene, linalool, alpha pinene, or a combination thereof.
  • the terpenes are derived from Cannabis spp. or an extract thereof.
  • the terpenes can be derived from any source and in certain embodiments, they can be present in steam distillate or an ethanolic extract of Cannabis sativa.
  • compositions in certain embodiments include extracts of Cannabis spp, such as C. sativa as a source of cannabinoids and/or terpenes.
  • the C. sativa comprises one or more of Ringo's Gift, Harle Tsu, ACDC, Charlotte's Web, The Gift, or Pineberry strains.
  • the C. sativa comprises the proprietary strain, APM, commercially-available from Apollon Formularies.
  • the edible or medicinal mushroom comprises a species from the genus Ganoderma, the genus Hericium, or the genus Cordyceps.
  • These mushrooms are well-known edible and/or medicinal mushrooms with a long history of use. Without limiting the invention to any particular theory of operation, mushrooms, such as Reishi mushrooms, Lion's Mane, or Cordyceps contain hundreds of beneficial polysaccharide compounds (e.g. the long-chain sugars in mushroom cell-walls) and terpenes that are believed to have multiple beneficial neuropharmacological effects including on anxiety, mood, certain psychological disorders, and even seizures.
  • mushroom polysaccharides have been proposed to improve cognitive dysfunction in vivo. These mushroom polysaccharides have shown a protective effect on neurons - protecting them from apoptosis (cell death), and oxidative stress.
  • the polysaccharides and triterpene compounds, for example, in Reishi mushroom both exhibit significant neuroprotective effects against stress.
  • the polysaccharide content in Reishi mushroom, particularly the beta-1,3 D-glucan has been shown to up-regulate the production of certain lymphocytes, T-helper cells, T-killer cells, and macrophages.
  • the same glycan has also been shown to be involved with suppressing tumor necrosis factor (TNF- ⁇ ).
  • NGF nerve growth factor
  • compositions preferably comprise the benefits of such edible or medicinal mushroom(s) as Ganoderma lucidum, Hericium erinaceus, Cordyceps sinensis, C. militaris, C. liangshanensis, C. gunnii, or C. cicadicola.
  • the mushrooms can be present in the compositions as fresh mushrooms, as whole or partial mushrooms in lyophilized or dehydrated form, or as an extract or concentrate thereof, including as a hot or cold water extract of the mushroom, a dried powder, a partially purified fraction thereof, or a fully purified compound derived therefrom, or in any other convenient or useful form.
  • the compositions further comprise one or more additional or optional ingredients comprising at least one flavonoid, S- adenosylmethionine, methylfolate, omega-3 fatty acids, a B vitamin or a compound providing (directly or indirectly) a biologically-available form thereof, or vitamin D or a compound providing (directly or indirectly) a biologically- available form thereof.
  • compositions In terms of compounding the compositions, the skilled artisan will appreciate that methods of maximizing the efficacy of the composition such as by enhancing the bioavailability of one or more components, or by providing the components in optimized ratios, for example one component to another with which it interacts, or each component to the others in ratio(s) that optimize the absorption into the gut or bloodstream, or enhance the therapeutic effect of the composition. The skilled artisan will also understand that some information useful in improving the compounding may be obtained empirically.
  • the compositions, or one or more components thereof may be solubilized, micronized, provided as, for example, extracts, powders, lyophilized powders, concentrates, tinctures, essential oils, aqueous or lipid suspensions, emulsions, microemulsions, or nano-emulsions, or in whole or part as liposomal, vesicular, or other delivery systems.
  • the compounding or formulation of any of the compositions provided herein may be optimized for the intended delivery route.
  • compositions may be administered and delivered as pharmaceuticals, however, it is also contemplated that one or more of the compositions may be formulated for administration and delivery by oral routes that include as food and beverages, including solid, semisolid, and liquid foods, such as smoothies, shakes, pudding, broths, teas, and soups.
  • food and or beverage compositions can also include hot, cold, or even frozen foods (such as frozen desserts).
  • kits for treating a subject suffering from a psychological disorder comprise administering to the subject at least one therapeutically effective dose of a composition comprising one or more serotonergic psychedelics, one or more cannabinoids, one or more terpenes, and one or more edible or medical mushrooms or and extract, fraction, or isolate thereof.
  • a composition comprising one or more serotonergic psychedelics, one or more cannabinoids, one or more terpenes, and one or more edible or medical mushrooms or and extract, fraction, or isolate thereof.
  • the psychological disorder comprises a psychosis or psychotic events, or abnormal anxiety or depression.
  • composition for use in the methods is generally as described above for the first aspect.
  • description of the compositions above is incorporated by reference herein for purposes of the present methods.
  • compositions for use in the methods further comprise one or more optional ingredients comprising at least one flavonoid, S- adenosylmethionine, methylfolate, omega-3 fatty acids, a B vitamin or a compound providing (directly or indirectly) a biologically-available form thereof, or vitamin D or a compound providing (directly or indirectly) a biologically- available form thereof.
  • the methods further comprise one or more steps of administering an additional therapeutically effective dose of the composition.
  • the additional administering steps are performed on a periodic basis of any frequency or schedule.
  • the administration or dosing can conveniently be on e.g. a daily, thrice weekly, twice weekly, weekly, biweekly, monthly, bimonthly, quarterly, semi-annual, or annual basis.
  • the administration need not be the same over every period of time.
  • administration could be daily for a week, then weekly for a month.
  • the administration could be every 4 months for a year, then every 6 months thereafter.
  • the actual amount of the composition or dosage administration can vary.
  • a monthly dosage schedule could feature a dose of x for the first dosage each quarter, and a dose of 0.1x for the remaining months in each quarter.
  • the methods further comprise the step of periodically assessing one or more of the subject's medication levels, enzyme levels, psychological status, or other indicators of physiological or psychological health, in order to determine the periodic basis for administration.
  • compositions disclosed herein in the first aspect of this disclosure can be formulated without any serotonergic psychedelics to create "modified compositions".
  • modified compositions are particularly useful in administering to subjects in between doses of the compositions including the psychedelics. Because some subjects may require very infrequent dosing with the composition including a psychedelic, and because the modified compositions provide numerous benefits to subjects for the disorders, methods for doing so are therefore provided.
  • the methods comprise an additional treatment step in between each administering or dosing step using the compositions with a psychedelic.
  • the additional treatment step comprises providing to the subject a composition comprising one or more cannabinoids, one or more terpenes, one or more edible or medical mushrooms or and extract, fraction, or isolate thereof, and optionally, one or more of at least one flavonoid, S-adenosylmethionine, methylfolate, omega-3 fatty acids, or a B vitamin or vitamin D or a compound providing a biologically-available form thereof.
  • compositions via any useful route, including parenteral (intravenous, intra-arterial, intramuscular, intraperitoneal, or subcutaneous), oral, nasal, ocular, transmucosal (buccal, vaginal, or rectal), transdermal, or via inhalation.
  • parenteral intravenous, intra-arterial, intramuscular, intraperitoneal, or subcutaneous
  • oral nasal, ocular, transmucosal (buccal, vaginal, or rectal), transdermal, or via inhalation.
  • parenteral intravenous, intra-arterial, intramuscular, intraperitoneal, or subcutaneous
  • oral nasal, ocular, transmucosal (buccal, vaginal, or rectal), transdermal, or via inhalation.
  • transmucosal bonal, vaginal, or rectal
  • transdermal or via inhalation.
  • the compositions may be formulated and optimized for delivery by any means.
  • the route of dosing or administration of compositions can vary. For example, administration via one route may be useful when administering a larger dose and a different route may be useful for smaller doses. Or, administration via a particular route may be appropriate initially, with subsequent doses conveniently administered through another route.
  • compositions for use in treatment of a subject suffering from a psychological disorder using artificial intelligence are provided herein.
  • the methods generally comprise, for a psychological disorder of interest, or for a subject in need of therapeutic compositions for such disorder:
  • the psychological disorder comprises a psychosis or psychotic events, or abnormal anxiety or depression.
  • the data for the method are obtained from original experiments and / or reviews of the relevant scientific literature.
  • the artificial intelligence algorithm can comprise any useful software or algorithm approach capable of making the distinctions required.
  • the algorithm comprises a classification algorithm, a regression algorithm, a clustering algorithm, or a combination thereof.
  • the methods comprise a classification algorithm that is a naive Bayes algorithm, decision tree, random forest algorithm, Support Vector Machines, or K Nearest Neighbor algorithm.
  • the methods comprise a regression algorithm that is a liner regression, lasso regression, logistic regression, or multivariate regression.
  • the methods comprise a clustering algorithm that is a K-means clustering, fuzzy C-means algorithm, expectation-maximization algorithm, or hierarchical clustering algorithm.
  • compositions are designed to optimize the compositions, and that such optimization as set forth above can be with respect to each particular disorder.
  • the compositions can also be optimized for, and a profile of relevant compositions generated for each particular subject, e.g. for a 'personalized medicine' approach.
  • the methods comprising the additional step of providing subject-specific data comprising, e.g. initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), specific symptomology, or the like.
  • subject-specific data comprising, e.g. initial or subsequent blood work, enzyme test results, bioinformatic data (including measurements of e.g. the genome, transcriptome, proteome, metabolome, or any portion thereof, for a subject), specific symptomology, or the like.
  • the artificial intelligence algorithm is then used to further optimize the composition based on those data in addition to the disorder-specific data.
  • the optimized formulation of the compositions may also be changed based on data from the results from an initial treatment, subsequent treatment, or based on subsequent tests of the subject.
  • a further aspect of the invention provides methods for the treatment of a psychological disorder comprising the step of administering to a patient in need thereof a composition comprising at least one serotonergic psychedelic in combination with at least one cannabinoid and at least one terpene, and at least one edible or medicinal mushroom or extract thereof, wherein the at least one cannabinoid and at least one terpene is administered separately from, sequentially to, or simultaneously with the serotonergic psychedelic and edible or medicinal mushroom; and wherein the at least one edible or medicinal mushroom or extract thereof is also administered separately from, sequentially to, or simultaneously with the serotonergic psychedelic and cannabinoid.
  • the at least one serotonergic psychedelic comprises psilocybin or psilocin, or serotonergic metabolites, derivatives, or analogs thereof;
  • the at least one cannabinoid comprises CBD, CBG, CBN, and THC extracted from Cannabis sativa Ringo's Gift strain;
  • the at least one terpene comprises limonene, myrcene, beta- caryophyllene, linalool, alpha pinene, or a combination thereof;
  • the at least one edible or medicinal mushroom or extract thereof comprises an extract of Ganoderma lucidum, Hericium erinaceus, Cordyceps sinensis, C. militaris, C. liangshanensis, C. gunnii, or C. cicadicola.

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Abstract

L'invention concerne des compositions et des procédés pour le traitement de troubles psychologiques qui comprennent une psychose ou des événements psychotiques, ou une dépression ou une anxiété anormale. Les compositions comprennent généralement au moins un psychédélique sérotoninergique, au moins un cannabinoïde, au moins un terpène et au moins un champignon comestible ou médicinal ou un extrait de celui-ci. L'invention concerne également des procédés d'optimisation de compositions à l'aide d'algorithmes d'intelligence artificielle.
PCT/IB2021/057019 2020-07-21 2021-08-01 Compositions et méthodes de traitement de psychoses et de troubles psychotiques WO2022018709A1 (fr)

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US11453689B2 (en) 2020-02-04 2022-09-27 Mindset Pharma Inc. 3-pyrrolidine-indole derivatives as serotonergic psychedelic agents for the treatment of CNS disorders
US11905535B2 (en) 2019-10-01 2024-02-20 Empyrean Nueroscience, Inc. Genetic engineering of fungi to modulate tryptamine expression
US12060328B2 (en) 2022-03-04 2024-08-13 Reset Pharmaceuticals, Inc. Co-crystals or salts of psilocybin and methods of treatment therewith

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US20180221333A1 (en) * 2017-03-22 2018-08-09 Rise Research Inc Optimized cannabis-based aphrodisiac and mood enhancer
US20190350949A1 (en) * 2017-01-18 2019-11-21 Procare Beheer B.V. Psilocybin and/or psilocin in combination with cannabinoids and/or terpenes
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US20090110674A1 (en) * 2007-10-24 2009-04-30 Loizou Nicos C Health supplement
US20200054701A1 (en) * 2015-01-31 2020-02-20 Constance Therapeutics, Inc. Cannabis oil extracts and compositions
US20190350949A1 (en) * 2017-01-18 2019-11-21 Procare Beheer B.V. Psilocybin and/or psilocin in combination with cannabinoids and/or terpenes
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11905535B2 (en) 2019-10-01 2024-02-20 Empyrean Nueroscience, Inc. Genetic engineering of fungi to modulate tryptamine expression
US11453689B2 (en) 2020-02-04 2022-09-27 Mindset Pharma Inc. 3-pyrrolidine-indole derivatives as serotonergic psychedelic agents for the treatment of CNS disorders
US12054504B2 (en) 2020-02-04 2024-08-06 Mindset Pharma Inc. 3-pyrrolidine-indole derivatives as serotonergic psychedelic agents for the treatment of CNS disorders
US12060328B2 (en) 2022-03-04 2024-08-13 Reset Pharmaceuticals, Inc. Co-crystals or salts of psilocybin and methods of treatment therewith

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