WO2023230303A1 - Traitement de déclin cognitif lié à l'anesthésie et à la sédation - Google Patents

Traitement de déclin cognitif lié à l'anesthésie et à la sédation Download PDF

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WO2023230303A1
WO2023230303A1 PCT/US2023/023649 US2023023649W WO2023230303A1 WO 2023230303 A1 WO2023230303 A1 WO 2023230303A1 US 2023023649 W US2023023649 W US 2023023649W WO 2023230303 A1 WO2023230303 A1 WO 2023230303A1
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entheogen
subject
group
psilocybin
administration
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PCT/US2023/023649
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English (en)
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Leonard LERER
Bernard Lerer
Karin BLAKOLMER
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Lerer Leonard
Bernard Lerer
Blakolmer Karin
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Publication of WO2023230303A1 publication Critical patent/WO2023230303A1/fr

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    • 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
    • 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
    • A61K31/395—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

Definitions

  • the present invention relates to the use of entheogens to reduce or ameliorate cognitive decline related to anesthesia or sedation or increase the resilience of patients to the stresses of surgery including physical and psychological sequelae of anesthesia and sedation and the underlying conditions requiring anesthesia or sedation.
  • Postoperative neurocognitive disorders is an overarching term that includes postoperative delirium, an acute state of confusion and inattention; and postoperative cognitive dysfunction (POCD), a prolonged state of cognitive impairment that predominantly affects higher-level cognitive skills and memory.
  • Proposed potential mechanisms for postoperative neurocognitive decline are speculative but include neuroinflammation as a result of perioperative stress, vascular disorders, or the acceleration of neurocognitive decline in patients with a previously undiagnosed neurodegenerative disorder (Mahanna-GabrielliE, SchenningKJ, ErikssonLI, et al. State of the clinical science of perioperative brain health. Br J Anae sth. 2019;123(4):464-478).
  • Entheogens are chemical substances, originating from fungi, plants and animals, that have been ingested for thousands of years for religious or spiritual purposes to produce an altered state of consciousness (Nichols DE: Psychedelics. Pharmacol Rev. 2016 Apr; 68(2): 264-355).
  • entheogens such as psilocybin
  • psilocybin for the treatment of mental health disorders (Geiger HA, Wurst MG et al: DARK Classics in chemical neuroscience. Psilocybin. ACS Chem. Neurosci.).
  • Psilocybin is a naturally occurring psychedelic compound produced by over 200 mushrooms, that is being researched as treatment for a range of psychiatric disorders (Carhart- Harris RL and Goodwin GM. (2017) The therapeutic potential of psychedelic drugs: past, present and future. Neuropsychopharmacology). Five separate trials have reported improvements in depressive symptoms after psilocybin-assisted psychotherapy including in 'treatment-resistant depression' (Carhart-Harris R, Giribaldi B, Watts R et al Trial of Psilocybin versus Escital opram for Depression ⁇ Engl J Med.
  • ketamine and psychedelics [including psilocybin, lysergic acid diethylamide (LSD), 5-MeO-DMT and N, N- dimethyltryptamine (DMT)] induce synaptic, structural, and functional changes, particularly in pyramidal neurons in the prefrontal cortex (David E. Olson: Biochemical Mechanisms Underlying Psychedelic- Induced Neuroplasticity Biochemistry 2022 61 (3), 127-136. DOI: 10.1021/acs.biochem.lc00812).
  • the present invention relates to the use of entheogens to reduce or ameliorate cognitive decline related to anesthesia or sedation or increase the resilience of patients to the stresses of surgery including physical and psychological sequelae of anesthesia and sedation and the underlying conditions requiring anesthesia or sedation.
  • the present invention provides methods of treating a subject comprising administering an entheogen or composition comprising an entheogen to a subject in an unconscious or semi-conscious state or about to be rendered in an unconscious or semi-conscious state.
  • the present invention provides entheogens or entheogen compositions for use in treating a condition associated with being in an unconscious or semiconscious state.
  • the unconscious or semiconscious state is caused by a modality selected from the group consisting of medically induced unconsciousness or semiconsciousness, trauma induced unconsciousness or semi-consciousness, illness induced unconsciousness or semi-consciousness, and condition induced unconsciousness or semiconsciousness.
  • the medically induced unconsciousness or semiconsciousness is induced by administration of an agent selected from the group consisting of an anesthetic and a sedative.
  • the anesthetic administered to the subject is selected from the group consisting of a general anesthetic agent delivered intravenously selected form the group consisting of propofol, etomidate, ketamine, methohexital and thiopental and a general anesthetic agent delivered via inhalation selected form the group consisting of sevoflurane, desflurane, and isoflurane.
  • the general anesthetic agent is administered with a adjuvant.
  • the adjuvant is selected from the group consisting of an opioid, a2-agonist, and NMDA receptor antagonist.
  • the adjuvant is selected from the group consisting of fentanyl, lidocaine, midazolam, dexamethasone, and dexmedetomidine.
  • the sedative administered to the subject is selected from the group consisting of a benzodiazepine, an a2- agonist, an opioid, ketamine and nitrous oxide.
  • the benzodiazepine is selected from the group consisting of diazepam, midazolam and lorazepam.
  • the neuroleptic agent is selected from the group consisting of haloperidol, droperidol, and phenothiazine.
  • the a2-agonist is clonidine.
  • administration of the entheogen inhibits, reduces or prevents cognitive decline related to anesthesia and/or sedation.
  • administration of the entheogen increases the resilience of patients to the stresses of surgery and anesthesia including physical and psychological sequelae of anesthesia and/or sedation.
  • administration of the entheogen improves cognitive recovery, and prevents or reduces reactive depression or prevents or reduces PTSD in subject following being in the unconscious or semi-conscious state.
  • the subject in an unconscious or semi-conscious state or about to be rendered in an unconscious or semi-conscious state is subject to heart surgery or surgery for major trauma.
  • the subject is in an intensive care unit.
  • the subject in an unconscious or semi-conscious state or about to be rendered in an unconscious or semi-conscious state is subject to an obstetrical intervention.
  • administration of the entheogen reduces or prevents post-natal depression.
  • administration of the entheogen inhibits, reduces or prevents a condition in the subject selected from the group consisting of post-traumatic stress disorder, depression, obsessive-compulsive disorder, an addictive disorder, and schizophrenia.
  • administration of the entheogen improves cognitive function or neuroplasticity in the subject.
  • the entheogen is psilocybin. In some preferred embodiments, the entheogen composition comprises psilocybin. In some preferred embodiments, the entheogen composition is a combination psilocybin and one or more compounds selected from the group consisting of psilocybin, baeocystin, aurugeniscin, norpsilocin, and norbaeocystin.
  • the entheogen composition is a mushroom extract composition comprising one or more compounds selected from the group consisting of psilocybin, baeocystin, aurugeniscin, norpsilocin, and norbaeocystin.
  • the mushroom extract is free of psilocybin.
  • the entheogen is 5-rnethoxy-N,N-dimethyltryptamine (5- MeO-DMT).
  • the entheogen composition comprises 5-methoxy- N,N-dimethyltryptamine (5 -MeO-DMT) .
  • entheogen is provided in a psychedelic dose.
  • the entheogen is provided in a sub-psychedelic dose.
  • the entheogen is administered intravenously.
  • the entheogen is co-administered with a 5-HT1 A agonist.
  • 5-HT1A agonist is buspirone.
  • a “patient,” “subject,” or “individual” are used interchangeably and refer to either a human or a non-human animal. These terms include mammals, such as humans, primates, livestock animals (including bovines, porcines, etc.), companion animals (e.g., canines, felines, etc.) and rodents (e.g., mice and rats).
  • administering or "administration of a substance, a compound or an agent to a subject can be carried out using one of a variety of methods known to those skilled in the art.
  • a PBP can be administered, intravenously, arterially, intradermally, intra-muscularly, intraperitonealy, intravenously, subcutaneously, sublingually, orally (by ingestion), intranasally (by inhalation), intrapulmonary (by nebulization or instillation) intraspinally, intracerebrally, and transdermally (by absorption, e.g., through a skin duct).
  • a compound or agent can also appropriately be introduced by rechargeable or biodegradable polymeric devices or other devices, e.g., patches and pumps, or formulations, which provide for the extended, slow or controlled release of the compound or agent.
  • Administering can also be performed, for example, once, a plurality of times, and/or over one or more extended periods.
  • the administration includes both direct administration, including self-administration, and indirect administration, including the act of prescribing a drug.
  • a physician who instructs a patient to self-administer a drug, or to have the drug administered by another and/or who provides a patient with a prescription for a drug is administering the drug to the patient.
  • a “therapeutically effective amount” or a “therapeutically effective dose” of a drug or agent, such as the entheogen compositions described herein, is an amount of a drug or an agent that, when administered to a subject will have the intended therapeutic effect.
  • the full therapeutic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses.
  • a therapeutically effective amount may be administered in one or more administrations.
  • the precise effective amount needed for a subject will depend upon, for example, the subject's size, health and age, the nature and extent of symptoms of the condition being treated. The skilled worker can readily determine the effective amount for a given situation by routine experimentation.
  • a “prophylactically effective amount” or a “prophylactically effective dose” of a drug or agent, such as an entheogen composition is an amount of a drug or an agent that, when administered to a subject will have the intended prophylactic effect.
  • the full prophylactic effect does not necessarily occur by administration of one dose, and may occur only after administration of a series of doses.
  • a prophylactically effective amount may be administered in one or more administrations.
  • the precise effective amount needed for a subject will depend upon, for example, the subject's size, health and age, the nature and extent of symptoms of the condition being treated. The skilled worker can readily determine the effective amount for a given situation by routine experimentation.
  • Treating” a condition or patient refers to taking steps to obtain beneficial or desired results, including clinical results.
  • Beneficial or desired clinical results include, but are not limited to, alleviation, amelioration, or slowing the progression, of one or more symptoms associated with the disease or disorder being treated.
  • treatment may be prophylactic.
  • the present invention relates to the use of entheogens to reduce or ameliorate cognitive decline related to anesthesia or sedation or increase the resilience of patients to the stresses of surgery including physical and psychological sequelae of anesthesia and sedation and the underlying conditions requiring anesthesia or sedation.
  • Entheogens are naturally occurring compounds with psychedelic properties that have historically been used for religious and spiritual ceremonies and also for medicinal purposes. In spite of legal barriers, there is rapidly increasing interest among clinicians and researchers in the use of natural or synthetic psychedelics for the treatment of psychiatric disorders.
  • the present invention provides methods of using psilocybin and other fungal/plant/animal-derived entheogens in different formulations (including IV), dosages and schedules in semi-conscious and unconscious (including medically induced, trauma-induced, illness or condition-induced) states to prevent and treat a range of conditions including psychiatric conditions (including PTSD, depression and OCD and addictive disorders, schizophrenia etc.) and to specifically prevent and treat cognitive decline related to anesthesia and sedation or increase the resilience of patients to the stresses of surgery and anesthesia including physical and psychological sequelae of anesthesia and sedation.
  • psychiatric conditions including PTSD, depression and OCD and addictive disorders, schizophrenia etc.
  • Semiconscious and unconscious states may be induced by, anesthesia, sedation, drugs, trauma, vegetative states, hyperthermia, hypothermia, Electro-Convulsive-Therapy, major surgery, medically induced coma, drug induced coma, cardiac arrest, asphyxia, prematurity, psychiatric conditions, etc.
  • an anesthetic agent administered to the subject is a general anesthetic agent delivered intravenously selected form the group consisting of propofol, etomidate, ketamine, methohexital and thiopental or a general anesthetic agent delivered via inhalation selected form the group consisting of sevoflurane, desflurane, and isoflurane.
  • one or more adjuvants are administered with the general anesthetic agent. Suitable adjuvants include, but are not limited to, opioids, a2-agonists, NMD A receptor antagonists.
  • the adjuvant is selected from the group consisting of opioid agents (e.g., morphine or fentanyl), lidocaine, midazolam, dexamethasone, and dexmedetomidine.
  • a sedative administered to the subject is a benzodiazepine, a2-agonists (e.g., clonidine), opioid (neuroleptic agents (e.g., haloperidol, droperidol, phenothiazines), ketamine or nitrous oxide.
  • a2-agonists e.g., clonidine
  • opioid neuropeptide
  • neutral agents e.g., haloperidol, droperidol, phenothiazines
  • ketamine nitrous oxide
  • the benzodiazepine is selected from the group consisting of diazepam, midazolam and lorazepam.
  • the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens pre- or during anesthesia for example in patients being operated on for heart disease or major trauma with the specific purpose of improving cognitive recovery and preventing reactive depression or PTSD.
  • the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens pre- or during obstetrical interventions such as Caesarian section in order to prevent post-natal depression.
  • the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens to patients in a semi-conscious or unconscious state in critical care and ICU settings over various periods of time in order to improve cognitive and other outcomes and prevent depression and PTSD.
  • administration e.g., intravenous administration
  • psilocybin or other entheogens to patients in a semi-conscious or unconscious state in critical care and ICU settings over various periods of time in order to improve cognitive and other outcomes and prevent depression and PTSD.
  • the methods comprise administration (e.g., intravenous administration) of psilocybin or other entheogens to these patients in a semi-conscious or unconscious state to improve outcome in terms of cognitive function (improving neuroplasticity) and the prevention of depression, OCD and other negative psychological outcomes.
  • administration e.g., intravenous administration
  • psilocybin or other entheogens to these patients in a semi-conscious or unconscious state to improve outcome in terms of cognitive function (improving neuroplasticity) and the prevention of depression, OCD and other negative psychological outcomes.
  • the present invention is not limited to any particular mechanism of action. Indeed, a mechanism of action is not necessary to practice the present invention. Nevertheless, it is contemplated that psilocybin or other entheogens play a prophylactic ( or therapeutic) role in the management of unconscious or semi-conscious patents in a similar manner to antacids (prevention of gastric damage) and antibiotics (prevention of infection) and anti -coagulants (prevention of hemorrhagic disorders) are generally used in operating rooms and critical care settings as preventive modalities.
  • the psilocybin and entheogens are administered as prophylaxis against cognitive decline and negative psychological outcomes such as depression and PTSD associated with the underlying condition that required anesthesia or sedation and/or caused an unconscious or semi-conscious state.
  • Preferred entheogens for use in the present invention include those derived from mushrooms, including psilocybin, alone or in combination with one or more of baeocystin, aurugeniscin, norpsilocin, norbaeocystin, as well as 5-methoxy-N,N-dimethyltryptamine (5- MeO-DMT).
  • the entheogen compositions may be prepared by a variety of methods including, but not limited to, chemical synthesis, extraction and/or purification from plants or fungi, and extraction and/or purification from mushroom cell cultures.
  • the entheogen compositions comprise psilocybin.
  • the entheogen compositions comprise psilocybin and additionally one or more compounds selected from the group consisting of baeocystin, aeruginascin, norpsilocin, norbaeocystin, and combinations thereof.
  • the entheogen composition comprises one or more compounds selected from the group consisting of baeocystin, aeruginascin, norpsilocin, norbaeocystin, and combinations thereof and is essentially free of psilocybin.
  • Exemplary entheogen compositions are provided below.
  • the compounds listed may, for example, be chemically synthesized (see, e.g., Sherwood et al., (2020) Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin; J. Nat. Prod. 83(2) 461-67, incorporated herein by reference in its entirety), may be provided in an extract from mushrooms or from mushroom cell cultures as described in detail below, or be isolated from mushrooms or mushroom cell cultures as described in detail below.
  • he listed composition comprises the listed compounds.
  • the listed compositions consist essentially of the listed compounds.
  • the listed compositions consist of the listed compounds.
  • composition Compounds in composition
  • baeocystin 15 baeocystin, aeruginascin, norpsilocin, norbaeocystin
  • baeocystin 16 baeocystin 17. baeocystin, aeruginascin
  • Biotechnology -based production of entheogens offers a promising route to ensure a cost- effective, cGMP, robust supply for clinical development.
  • Naturally derived psychedelic compounds may offer significant therapeutic advantages over synthetic molecules because of entourage effects. These reflect the action of additional components that may act synergistically or additively with the principal molecule or have pharmacokinetic effects.
  • additional components may act synergistically or additively with the principal molecule or have pharmacokinetic effects.
  • psilocybin which is derived from multiple mushroom species that contain a wealth of additional active components.
  • Anecdotal and clinical reports as well as preclinical studies suggest a discernible difference between the effects of chemically synthesized psilocybin and those of psychedelic mushrooms and also differences among the effects of different mushroom strains.
  • the entheogen compounds utilized in the present invention are derived from cell culture and in particular on mushroom cell cultured, psychoactive compound-containing mushroom compositions.
  • the term "mushroom culture compositions” refers to compositions comprising a mushroom cell culture and products derived therefrom specifically including 1) fractions, such as aqueous fractions, prepared from the mushroom cell culture that contain one or more psychoactive compounds, 2) extracts, such as aqueous solvent extracts or organic solvent extracts, prepared from the mushroom cell culture that comprise one or more psychoactive compounds, and 3) purified preparations of one or more psychoactive compounds prepared from a mushroom cell culture by methods including one or more of solvent extraction, concentration by solvent removal, chromatography and other methods of extraction, purification and fractionation.
  • neuroactive compounds refers to chemical substances that change a person's mental state by affecting the way the brain and nervous system work, and specifically, includes, but is not limited to psilocybin, baeocystin, aurugeniscin, norpsilocin, norbaeocystin, and combinations thereof.
  • the effective dosage of the mushroom cell culture compositions is a sub-psychedelic dose.
  • a "sub-psychedelic dose” as used herein is a sub-hallucinogenic doses of a psychedelic substance such as a psilocybin.
  • Sub-psychedelic dosing can be achieved via several schedules: 1) sub-chronic, sub-psychedelic doses of psilocybin given over several days with or without other components of mushroom cell culture extract, 2) a sustained release preparation of psilocybin with or without other components of the mushroom cell culture extract which will allow the full psychedelic dose to be administered over 24 hours and thus avoid acute psychotogenic effects; 3) a psychedelic dose of psilocybin with or without other components of mushroom cell culture spectrum extract in conjunction with a 5-HT2A receptor antagonist, that blocks psilocybin- induced psychedelic effects.
  • the biomass used to prepare a mushroom extract useful in the compositions of the present invention is any fungi (including hybrids) of part thereof (e.g., mycelia, primordia, fruiting bodies, etc.) containing the psilocybin biosynthetic gene cluster (psiD, psiH, psiK, psiM) or other mushrooms, fungi, lichens, etc. producing psilocybin or psilocybin analogs or related tryptamines.
  • the biomass is mycelial biomass.
  • Exemplary mushroom species include, but are not limited to, Conocybe sp., Copelandia sp., Galerina sp., Gerronema sp., Gymnopilus sp., Hypholoma sp., Inocybe sp., Mycena sp., Panaeolina sp., Panaeolus sp., Pluteus sp., andPsilocybe sp.
  • Exemplary Psilocybes include, but are not limited to, P. acutipilea, P. angustipleurocystidiata, P. antioquensis, P. aquamarine, P. argentipes, P.
  • cordispora P. cubensis, P. cyanescens, P. cyanofibrillosa, P. dumontii, P. eucalypta, P. fagicola, P. fagicola mesocystidiata, P. farinacea, P. fimetaria, P. fuliginosa, P. furtadoana, P. galindoi, P. goniospora, P. graveolens, P. guatapensis, P. guilartsis, P. heimii, P. heliconiae, P. herrerae, P. hispanica, P. hoogshagenii hoogshagenii, P.
  • pericystis P. pintonii, P. pleurocystidiosa, P. plutonia, P. portoricensis, P. pseudoaztecorum, P. puberula, P. quebecensis, P. ramulosa, P. rostrata, P. rzedowskii, P. samuiensis, P. sanctorum, P. schultesii, P. semilanceata, P. septentrionalis, P. serbica, P. sierrae, P. sylvatica, P. singerii, P. strictipes, P. stuntzii, P. subacutipilea, P.
  • the entheogen may be further formulated with one or more pharmaceutically acceptable carriers or delivery vehicles.
  • pharmaceutically acceptable carrier includes any and all solvents, dispersion media, coatings, surfactants, antioxidants, preservatives (e.g., antibacterial agents, antifungal agents), isotonic agents, absorption delaying agents, salts, preservatives, drugs, drug stabilizers, gels, binders, excipients, disintegration agents, lubricants, sweetening agents, flavoring agents, dyes, such like materials and combinations thereof, as would be known to one of ordinary skill in the art (see, for example, Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990, pp. 1289-1329, incorporated herein by reference). Except insofar as any conventional carrier is incompatible with the active ingredient, its use in the pharmaceutical compositions
  • the entheogens of the present invention may be formulated with different types of carriers depending on whether it is to be administered in solid, liquid or aerosol form, and whether it need to be sterile for such routes of administration as injection.
  • the cell extracts of the present invention can be administered intravenously, intradermally, transdermally, intrathecally, intraarterially, intraperitoneally, intranasally, intravaginally, intrarectally, topically, intramuscularly, subcutaneously, mucosally, orally, topically, locally, inhalation and nebulization (e.g., aerosol inhalation), injection, infusion, continuous infusion, localized perfusion bathing target cells directly, via a catheter, via a lavage, in cremes, in lipid compositions (e.g., liposomes), or by other method or any combination of the forgoing as would be known to one of ordinary skill in the art (see, for example, Remington's Pharmaceutical Sciences, 18th Ed. Mack Printing Company, 1990,
  • entheogens of the present invention will be administered in a manner compatible with the dosage formulation and in such amount as is therapeutically effective.
  • the formulations are easily administered in a variety of dosage forms such as formulated for parenteral administrations such as injectable solutions, or aerosols for delivery to the lungs, or formulated for alimentary administrations such as drug release capsules and the like.
  • the entheogens of the present invention suitable for administration is provided in a physiologically acceptable carrier with or without an inert diluent.
  • the carrier should be assimilable and includes liquid, semi-solid, i.e., pastes, or solid carriers. Except insofar as any conventional media, agent, diluent or carrier is detrimental to the recipient or to the therapeutic effectiveness of the composition contained therein, its use in administrable composition for use in practicing the methods of the present invention is appropriate.
  • carriers or diluents include fats, oils, water, saline solutions, lipids, liposomes, resins, binders, fillers and the like, or combinations thereof.
  • composition may also comprise various antioxidants to retard oxidation of one or more component. Additionally, the prevention of the action of microorganisms can be brought about by preservatives such as various antibacterial and antifungal agents, including but not limited to parabens (e.g., methylparabens, propylparabens), chlorobutanol, phenol, sorbic acid, thimerosal or combinations thereof.
  • parabens e.g., methylparabens, propylparabens
  • chlorobutanol phenol
  • sorbic acid thimerosal or combinations thereof.
  • the entheogens are combined with the carrier in any convenient and practical manner, i.e., by solution, suspension, emulsification, admixture, encapsulation, absorption and the like. Such procedures are routine for those skilled in the art.
  • Stabilizing agents can be also added in the mixing process in order to protect the composition from loss of therapeutic activity, i.e., denaturation in the stomach.
  • stabilizers for use in the composition include buffers, amino acids such as glycine and lysine, carbohydrates such as dextrose, mannose, galactose, fructose, lactose, sucrose, maltose, sorbitol, mannitol, etc.
  • the actual dosage amount of the entheogen of the present invention administered to an animal patient can be determined by physical and physiological factors such as body weight, severity of condition, the type of disease being treated, previous or concurrent therapeutic interventions, idiopathy of the patient and on the route of administration: Depending upon the dosage and the route of administration, the number of administrations of a preferred dosage and/or an effective amount may vary according to the response of the subject. The practitioner responsible for administration will, in any event, determine the concentration of active ingredient(s) in a composition and appropriate dose(s) for the individual subject.
  • zebrafish (Danio rerio , Drugs: Propofol is a short-acting hypnotic drug that produces a rapid anesthesia induction with short duration being rapidly metabolized and without cumulative effects, being also capable of causing cardiorespiratory depression.
  • FSME is “full spectrum” psychedelic mushroom extract - a purified, methanol extract of Psilocybe mushroom with precise quantitation of psilocybin and psilocin and tryptamines of the psilocybin biosynthetic chain (baeocystin, norbaeocystin, aerugenascin norpsilocin).
  • Treatment groups, dosing, experimental design Four groups: Control (tank water); propofol only; propofol plus FSME; FSME only. Dosing: FSME - 5mg/L; Propofol - 1.25mg/L.
  • mice Behavioral phenotyping is undertaken including the open field arena, novel object, social interaction, light-dark preference and other behavioral phenotyping tests. Other possible tests that may be conducted include brain metabolomics, brain synaptic proteins and microbiome metagenomics may be included. These experiments will subsequently be conducted in disease models for psychiatric and neurological disorders.

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Abstract

La présente invention concerne l'utilisation d'enthéogènes pour réduire ou améliorer le déclin cognitif lié à l'anesthésie ou à la sédation ou augmenter la résilience des patients aux stress de chirurgie comprenant les séquelles physiques et psychologiques de l'anesthésie et de la sédation et des affections sous-jacentes nécessitant une anesthésie ou une sédation.
PCT/US2023/023649 2022-05-27 2023-05-26 Traitement de déclin cognitif lié à l'anesthésie et à la sédation WO2023230303A1 (fr)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019226599A1 (fr) * 2018-05-22 2019-11-28 Alkalidx, Inc. Diagnostics et traitements de sujets insensibles à un anesthésique
WO2022082058A1 (fr) * 2020-10-16 2022-04-21 Eleusis Therapeutics Us, Inc. Méthode de traitement par alcaloïdes tryptamines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019226599A1 (fr) * 2018-05-22 2019-11-28 Alkalidx, Inc. Diagnostics et traitements de sujets insensibles à un anesthésique
WO2022082058A1 (fr) * 2020-10-16 2022-04-21 Eleusis Therapeutics Us, Inc. Méthode de traitement par alcaloïdes tryptamines

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