Treatment of long-term neurocognitive impairment

Abstract

Compounds and compositions for use in the treatment or prevention of long-term effects of neurological conditions in human or animal subjects. The compounds have neurotrophic activity and are preselec

Description

FIELD This disclosure relates to compounds, compositions, and methods for treating and preventing long-term neurological and neurocognitive effects and sequelae. Without limiting the generality of its possible applications, the disclosed technology may be beneficial for treating Long COVID. BACKGROUND WO2019 / 169165 relates to ketamine and certain ketamine-related compounds for use in the treatment of disorders, including neurological disorders, psychotic disorders, pain disorders, dementia, major depressive disorder, treatment-resistant depression, suicidal ideation, cognitive impairment associated with various neurological disorders and other conditions and diseases. EP3689340A1 discloses (R)-ketamine as a prophylactic or therapeutic agent for neurodegeneration disease and recognition functional disorder, but makes no reference to longterm disorders such as post-viral syndromes, infectious etiologies, or sequelae to infections. Several clinical trials have shown no benefit in preventing post-operative or post-injury neurocognitive decline after a single administration of Ketamine. WO2019160057 relates to a “Preventive or Therapeutic Agent and Pharmaceutical Composition for Inflammatory Diseases or Bone Diseases” and is silent on any post-viral neurological or other conditions. WO2020176599 discloses 5-HT2A modulators for increasing translation, transcription, or secretion of neurotrophic factors. It further discloses 8-methoxy-3-methyl-1,2,3,4,5,6-hexahydroazepino[4,5-B]indole (Tabernanthalog) - a derivative of ibogaine - for the treatment of certain neurological and psychiatric conditions and disorders. US 2018 / 0021326A1 discloses the use of a "stack" of treatment consisting of psilocybin, niacin and Lion's Mane mushroom extract for the treatment of a range of neurodegenerative and neurological conditions. NMDA receptor antagonists (competitive receptor antagonists, ion channel blockers, and glycine antagonists) selfotel, aptiganel, eliprodil, licostinel and gavestinel failed to show efficacy in clinical trials of stroke or traumatic brain injury. None of these agents have neurotrophic actions. The preceding discussion of the background is intended only to facilitate an understanding of the present disclosure. It should be appreciated that the discussion is not an acknowledgment or admission that any of the material referred to was part of the common general knowledge in the art as at the priority date of the application. SUMMARY According to an aspect of the disclosure there is provided a compound for use in the treatment or prevention of at least one long-term effect of a neurological condition in a human or animal subject, wherein said compound has neurotrophic activity and is preselected for its effectiveness to counter, inhibit or suppress excess central nervous system (CNS) quinolinic acid (QUIN) concentration levels in the subject. The neurological condition may comprise a long-term neurocognitive disorder associated with activation of the kynurenine pathway in the subject. The neurological condition may comprise a long-term adverse effect, long-term adverse health condition, or long-term sequela of activation of the kynurenine pathway in the subject. The neurological condition may be associated with long COVID. As used herein, the phrase “long-term” may be understood to mean a period of persistence or duration exceeding 28 days. It will be appreciated, however, that the phrase may mean other periods of time depending upon the specific neurological condition and typical period of persistence or duration of its effects. For purposes of the present disclosure, the term “excess” and variations such as “excessive”, when used in the context of QUIN formation and / or concentration, will be understood to mean a concentration of QUIN in cerebrospinal fluid of the subject which exceeds an upper limit of a normal reference range for a general population of such subjects. Normal cerebrospinal fluid levels in a human are below 50 nM, usually between 1 and 10 nM. Levels above 100 nM are considered cytotoxic. The range for normal and pathological concentrations varies slightly due to differences in the methods of measurement. In the present context, the upper level of the normal reference range for QUIN in one embodiment is considered to be about 40 nM. In certain embodiments, therefore, the compound having neurotrophic activity is preselected for its effectiveness to counter, inhibit, or suppress the effects of QUIN concentration levels above about 40 nM in cerebrospinal fluid of the subject. According to a further aspect of the disclosure there is provided a compound for use in a method of treating or preventing at least one long-term adverse health condition or sequela associated with a neurological condition in a human or animal subject, wherein said compound has neurotrophic activity and is preselected for its effectiveness to counter, inhibit or suppress excess quinolinic acid (QUIN) concentration levels in the subject. The disclosed technology extends to a pharmaceutical composition comprising said compound and at least one other compound having neurotrophic activity. The composition may be effective to counter, inhibit or suppress the effects of excessive QUIN formation as an ensemble or entourage of the at least two neurotrophic compounds. The at least two neurotrophic compounds in combination with each other may have a synergistic effect. The compound may be preselected and configured to suppress the effects of excessive QUIN formation due to increased metabolism in the kynurenine (KYN) pathway of tryptophan (Trp) degradation. Without limitation, the neurological condition may be selected from the group consisting of physiological impairments or deficits relating to cognitive function, executive function, planning, attention, complex attention, learning, working memory, declarative memory, long-term memory, processing speed, perceptual motor control, social cognition, self-awareness, attention, “brain fog” and fatigue. The neurological condition may be due to excessive CNS QUIN formation. The neurological condition may be associated with sequelae of infection, post-sepsis syndrome and post-intensive care syndrome. The neurological condition may comprise a physiological or psychological impairment or deficit secondary to a viral infection of a human or animal subject. The neurological condition may present with chronic neurological deficits or post-acute sequelae in the subject. Without limitation, the neurological condition may be associated with sequelae of infection of the subject by SARS-CoV-2 virus. In the disclosed pharmaceutical compositions comprising a combination or ensemble of multiple different types of compounds having neurotrophic activity, the respective types of compounds may be present in the composition in equal proportions. For example, in a composition containing two different types of compounds, the two different compounds may be present in a relative ratio of approximately 1:1 w / w. Instead, the respective types of compounds may be present in the disclosed pharmaceutical composition in different proportions. For example, in a composition containing two different types of compounds, the two different compounds may be present in a relative ratio between 1:1 w / w and 1:100 w / w. The disclosure extends to the use of the compound or composition described above in the manufacture of a medicament for use in the treatment or prevention of a long-term adverse health condition or sequela associated with a neurological condition. The long-term condition or sequela may be secondary to a viral infection as described above. According to a further aspect of the disclosure there is provided a compound for use in a method of treating at least one adverse health condition or sequela associated with a neurological condition in a human or animal subject, wherein the compound has neurotrophic activity. The compound may further be preselected for its effectiveness to counter, inhibit or suppress excess CNS quinolinic acid (QUIN) concentration levels in the subject. The disclosure extends to the use of a compound having neurotrophic activity for the treatment of at least one adverse health condition associated with a neurological condition in a human or animal subject. The compound may further be preselected for its effectiveness to counter, inhibit or suppress excess CNS quinolinic acid (QUIN) concentration levels in the subject. The disclosure extends to a compound having neurotrophic activity for use in the manufacture of a medicament for the treatment of at least one adverse health condition associated with a neurological condition in a human or animal subject. The compound may further be preselected for its effectiveness to counter, inhibit or suppress excess CNS quinolinic acid (QUIN) concentration levels in the subject. The disclosure extends to a pharmaceutical composition as described above for use in a method of treating at least one neurocognitive disorder, adverse health condition or sequela associated with a neurological condition. The disclosed compound or pharmaceutical composition may be formulated in a single dosage form containing a microdose of at least one of the compounds having neurotrophic activity. The disclosure extends to a pharmaceutical composition formulated in a single dosage form for use in a method of treating a neurological condition or at least one adverse health condition or sequela associated with a neurological condition in a human or animal subject, wherein the single dosage form contains a microdose of at least one compound having neurotrophic activity. The compound may further be preselected for its effectiveness to counter, inhibit or suppress the effects of excess quinolinic acid (QUIN) concentration levels in the subject. The microdose may comprise a dose of said compound in a range between 0% and 15% of a pharmacologically active dose of the compound. The microdose may comprise a dose of said compound in a range from about 1% to 10% of the pharmacologically active dose of the compound. The microdose may comprise about 10% of the pharmacologically active dose of the compound. For single dosage forms containing more than one type of compound having neurotrophic activity, each such compound may be present in an amount approaching the lower end of each of the stated microdose ranges. This may be appropriate in view of the expected summation of the potential adverse and beneficial effects of the compounds making up the ensemble. The pharmaceutical composition may contain another medical ingredient. The other medical ingredient may comprise lithium. Instead, on in addition, the other medical ingredient may comprise a tricyclic antidepressant agent, for example imipramine; or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of imipramine or any of its enantiomers. The other medical ingredient may comprise naltrexone or naloxone. The other medical ingredient may comprise memantine. The other medical ingredient may comprise riluzole. The other medical ingredient may comprise lanicemine. The other medical ingredient may comprise rislenemdaz. The other medical ingredient may comprise esmethadone. The other medical ingredient may comprise minocycline. The other medical ingredient may comprise melatonin. The other medical ingredient may comprise butyrate. The other medical ingredient may comprise an anti-inflammatory agent, such as aspirin, non-steroidal antiinflammatory drugs or COX-2 inhibitors. The other medical ingredient may comprise galantamine. The adverse health condition may comprise a prolonged or long-term adverse effect or sequela of activation of the KYN pathway, i.e., it may comprise a condition associated with excessive QUIN. The adverse health condition may comprise such an effect that persists for more than 28 days after an incident or disease process leading to activation of the KYN pathway and excess CNS production of QUIN. The adverse health condition may be secondary to a neurological condition due to excess QUIN formation or concentration levels in the subject. The adverse health condition may be associated with sequelae of infection, post-sepsis syndrome and post-intensive care syndrome. The neurological condition may comprise a physiological or psychological impairment or deficit secondary to a viral infection of a human or animal subject. The neurological condition may present with chronic neurological deficits or post-acute sequelae in the subject. Without limitation, the neurological condition may be associated with sequelae of infection of the subject by at least one virus as described above. The neurological condition may be associated with long COVID. The neurological condition may be associated with sequelae of infection of the subject by SARS-CoV-2. The adverse health condition may be secondary to a neurological condition due to excess QUIN formation or concentration levels in the subject. The adverse health condition may be associated with long COVID. The adverse health condition may be associated with sequelae of infection of the subject by SARS-CoV-2. The disclosure extends to a composition containing the compound in an amount effective for reducing the symptoms of said adverse health condition associated with a neurological condition in a human or animal subject due to excess QUIN concentration levels, for use in a method of treating or preventing said adverse health condition. The adverse health condition may comprise a prolonged or long-term adverse effect as described above. The disclosure extends to the use of a compound having neurotrophic activity for the treatment or prevention of an adverse health condition associated with a neurological condition in a human or animal subject due to excess QUIN concentration levels. The adverse health condition may comprise a prolonged or long-term adverse effect as described herein. The disclosure extends to a compound having neurotrophic activity for use in the manufacture of a medicament for the treatment or prevention of an adverse health condition associated with a neurological condition due to excess QUIN. The adverse health condition may comprise a prolonged or long-term adverse effect as described above. According to a further aspect of the disclosure there is provided a method of treating or preventing at least one adverse health condition or sequela associated with a neurological condition, the method comprising a step of administering to a human or animal subject in need thereof a therapeutically effective amount of a compound having neurotrophic activity. The compound may further be preselected for its effectiveness to counter, inhibit or suppress excess quinolinic acid (QUIN) concentration levels in the subject. The compound, the adverse health condition or sequela, and the neurological condition may be as described above. The neurological condition may be due to excess QUIN. The neurological condition may be associated with long COVID. In each of the aspects of the technology described herein, the compound having neurotrophic activity may be represented by the following formula: [CHEM. 1] wherein: X is independently selected from the group consisting of a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted aryl; and Ri is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted aryl; and any combination of the foregoing. The compound having neurotrophic activity may be selected from the group consisting of ketamine, (R)-ketamine, R(-)-ketamine, (S)-ketamine, S(+)-ketamine, (R)-norketamine, (2R,6R)-hydroxynorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (R)-dehydronorketamine, (S)-dehydronorketamine, pharmacologically acceptable salts thereof; and any combination of the foregoing. The compound having neurotrophic activity may be selected from the group consisting of enantiomers of any of the foregoing compounds; pharmacologically acceptable salts, solvates, hydrates, primary metabolites thereof, and any combination of the foregoing. 5 The compound having neurotrophic activity may accordingly comprise (R)-ketamine or a pharmacologically acceptable salt thereof. The compound may comprise a solvate, hydrate, primary metabolite or metabolite, or prodrug thereof. Instead, the compound in each aspect of the disclosure may comprise a serotonergic psychedelic. The serotonergic psychedelic may comprise psilocybin, or any of its enantiomers, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of psilocybin or any of its enantiomers or lysergic acid diethylamide (LSD) or / V,A / -Dimethyltryptamine (DMT) or 5-methoxy- / V,A / -dimethyltryptamine (5-MeO-DMT) or an enantiomer thereof or 2,5-Dimethoxy-4-iodoamphetamine (DOI) or an enantiomer thereof. Instead, the neurotrophic compound may comprise a psychoactive indole alkaloid. The compound may comprise ibogaine or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of ibogaine or any one of its enantiomers. The primary metabolite may comprise noribogaine. The neurotrophic compound may comprise tabernanthalog. The disclosed composition may in each case comprise a combination of two or more of the following compounds (i) to (xxiv) or pharmacologically acceptable enantiomers, salts, solvates or hydrates thereof: i. ketamine, (R)-ketamine, R(-)-ketamine, (S)-ketamine, or S(+)-ketamine; ii. (R)-norketamine, (2R,6R)-hydroxynorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (R)-dehydronorketamine or (S)-dehydronorketamine; iii. Psilocybin or psilocin; iv. lysergic acid diethylamide (LSD); v. A / ,A / -dimethyltryptamine (DMT); vi. 5-methoxy- / V, / \ / -dimethyltryptamine (5-MeO-DMT); vii. 2,5-dimethoxy-4-iodoamphetamine (DOI); viii. ibogaine or noribogaine; ix. tabernanthalog; x. lithium; xi. tricyclic antidepressant agents; xii. naltrexone; xiii. naloxone; xiv. memantine; XV. riluzole; xvi. lanicemine; xvii. rislenemdaz; xviii. esmethadone; xix. minocycline; XX. melatonin; xxi. butyrate; xxii. anti-inflammatory agents; xxiii. COX-2 inhibitors; and xxiv. galantamine. In one embodiment, the composition may comprise any one of the compounds (i) to (iii) in combination with at least one of the compounds (iv) to (xxiv). For parallel subsets of the technology described and claimed herein, corresponding embodiments or modes of performance are applicable to each of the parallel subsets. For example, and without limitation thereto, the neurological condition or adverse health condition to be treated or prevented may in each case be associated with long COVID and / or sequelae of infection of the subject by SARS-CoV-2. Embodiments and modes of performing the disclosed technology will now be described by way of example only. 5 DETAILED DESCRIPTION Embodiments of the disclosed compounds, compositions and methods for treatment or prevention of the effects of neurological conditions, neurocognitive disorders and adverse health conditions are explained in greater detail in the following description. 10 Several acquired disease processes negatively affect neurocognitive function. The development of the technology disclosed herein followed an inventive appreciation by tbe inventor that these processes have in common activation of immune and metabolic processes which culminate in overactivation of the kynurenine (KYN) pathway of tryptophan (Trp) metabolism, resulting in 15 excessive formation of quinolinic acid (QUIN). The excessive production of QUIN is a result of both increased formation due to increased flux of Trp via the KYN pathway and decreased metabolism of excess QUIN. QUIN is essential for the formation of the coenzyme nicotinamide adenine dinucleotide (NAD+) via the KYN pathway. NAD+ is involved in several critical intracellular processes by enabling electron transfer, acting as a substrate for enzymes and facilitating posttranslational modifications to metabolites. During pathological conditions excessive QUIN is formed by microglia and infiltrating macrophages. Under these circumstances QUIN acts as a neurotoxin via several mechanisms. Negative effects of excessive QUIN include excitotoxicity due to overstimulation of N-methyl-D-aspartate (NMDA) receptors, pro-inflammatory effects, pro-oxidant effects and increases in reactive radical metabolites and via disruption of the blood-brain barrier. The enzyme quinolinate phosphoribosyltransferase (QPRT) converts QUIN into nicotinic acid mononucleotide (NAMN), which is subsequently converted to NAD+. Inhibition of QPRT causes increases in QUIN, leading to neurotoxic effects. Inflammatory cytokines, including IFN-Y, oxidative stress from radicals, excessive glutamate (Glu) and QUIN itself can inhibit QPRT, thereby setting up a toxic cycle leading to ever increasing levels of QUIN. Aspects of the present disclosure provide a compound for use in the treatment or prevention of long-term effects of neurological conditions, or long-term adverse health conditions or sequelae of neurological conditions, in human or animal subjects. The compound may be characterized by having neurotrophic activity. The compound may be preselected for its effectiveness to counter, inhibit or suppress excess quinolinic acid (QUIN) concentration levels or formation in humans and / or animals. The neurological condition may be associated with long COVID. The neurological condition may be associated with sequelae of infection of the subject by SARS-CoV-2. The compound having neurotrophic activity may be preselected for its effectiveness to inhibit cerebrospinal fluid quinolinic acid (QUIN) concentration levels above 40 nM. In further embodiments, the upper level of the normal range is considered to be about 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95,100 or 105 nM. The compound may be selected accordingly for its inhibitory effectiveness. The disclosure extends to a composition for use in a method of treating or preventing a neurological condition due to excess QUIN, wherein the composition contains a compound having neurotrophic activity, in an amount effective for reducing the symptoms of a neurological condition due to excess QUIN. The disclosure extends to the use of a compound having neurotrophic activity, for the treatment or prevention of a neurological condition due to excess QUIN. The disclosure extends to a compound having neurotrophic activity for use in the manufacture of a medicament for the treatment or prevention of a neurological condition due to excess QUIN. In a further aspect, the disclosure provides a compound for use in the treatment or prevention of at least one long-term effect of a condition characterised by excess QUIN formation as described above. The compound may be characterized by having neurotrophic activity. The disclosure also provides a compound for use in a method of treating or preventing at least one adverse health condition associated with a neurological condition, for example, a neurological condition due to excess QUIN. The compound may have neurotrophic activity. The adverse health condition may be secondary to a neurological condition due to excess QUIN concentration levels or formation. The adverse health condition may be associated with sequelae of infection of the subject by one or more viruses selected from the group consisting of SARS-CoV-2, SARS-CoV-1, MERS-CoV, Human immunodeficiency virus (HIV), Zika virus, Influenza virus, Highly Pathogenic Avian Influenza virus, Bovine Influenza virus, Epsteinn-Barr virus, and Coxsackie virus. The adverse health condition may be associated with sequelae of infection of a patient by one or more bacteria selected from the group consisting of Gram-negative bacteria, Borrelia burgdorferi, Mycobacterium tuberculosis, Streptococcus, Staphylococcus, Listeria, Haemophilus, Neisseria, Pseudomonas, Escherichia, including sepsis caused by these organisms, or any other organism. The adverse health condition may be associated with sequelae of infection of a patient by one or more protozoa selected from the group consisting of Amoeba, Entamoeba, Giardia, Rhizopoda, Acanthamoeba, Sarcodina, Plasmodium, Trypanosoma. The adverse health condition may be associated with sequelae of infection of a patient by one or more fungi selected from the group consisting of Cryptococcus, Aspergilloses, Coccidioides, Histoplasma, Blastomyces, Mucormycoses, Pneumocystis, Zycomycosis and Paracoccidioides. The adverse health condition may be associated with sequelae of surgery, including post-operative neurocognitive impairment or decline. The adverse health condition may be associated with sequelae of trauma selected from the group consisting of polytrauma, fractures, blunt trauma, penetrating trauma, and head injury, including, but not limited to concussion, post-concussion syndrome, second hit syndrome, chronic traumatic encephalopathy, or penetrating brain injury. The adverse health condition may be associated with sequelae of post-cardiac arrest brain injury. The adverse health condition may be associated with sequelae of spinal injury, including, but not limited to spinal cord injury, penetrating spinal cord injury, or neuropraxia. The adverse health condition may be associated with sequelae of cerebral hemorrhage, including, but not limited to extradural and subdural hemorrhage, intra-cerebral hemorrhage, cerebral thrombosis, or ischemic cerebral damage. The adverse health condition may be associated with sequelae of chemotherapy, including “chemo brain”. The adverse health condition may be associated with sequelae of immunotherapy, including, but not limited to treatment with Interferons, including Interferon a, antibodies and immunomodulators. The adverse health condition may be associated with sequelae of one or more auto-immune diseases, including, but not limited to, Crohn’s Disease, Ulcerative Colitis, inflammatory bowel disease, Behcet’s disease, systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren’s syndrome, Celiac disease, auto-immune thyroiditis and Grave’s disease. The adverse health condition may be associated with sequelae of radiation treatment, brain radiation, or post radiation exposure. The adverse health condition may be associated with sequelae of neurocognitive impairment associated with morbid obesity. The adverse health condition may comprise a prolonged or long-term adverse effect of a condition characterized by excess QUIN formation as described above, i.e., a condition associated with a neurological condition due to excess CNS QUIN concentration levels. The disclosure extends to a composition containing the compound in an amount effective for reducing the symptoms of said adverse health condition associated with a neurological condition due to excess CNS QUIN, for use in a method of treating or preventing said adverse health condition. The adverse health condition may comprise a prolonged or long-term adverse effect as described above. The disclosure extends to the use of a compound having neurotrophic activity for the treatment or prevention of an adverse health condition associated with a neurological condition due to excess CNS QUIN. The adverse health condition may comprise a prolonged or long-term adverse effect as described above. The disclosure extends to a compound having neurotrophic activity for use in the manufacture of a medicament for the treatment or prevention of an adverse health condition associated with a neurological condition due to excess CNS QUIN. The adverse health condition may comprise a prolonged or long-term adverse effect as described above. The adverse health condition may be secondary to a neurological condition due to excess QUIN. The adverse health condition may be associated with sequelae of a condition characterized by excess CNS QUIN formation as described above. The adverse health condition may be selected from the group consisting of: cognitive dysfunctions; cognitive decline; cognitive deficits; attention deficits; neurological disorders; neuroinflammatory and other inflammatory conditions resulting from a condition characterized by excess CNS QUIN formation as described above; conditions caused by activation of pro-inflammatory microglia; diseases exhibiting neurological sequelae of infection; dysautonomia; long-term brainstem damage and symptoms caused by dysautonomia; loss of smell (anosmia); altered sense of smell (parosmia); presence of smell in the absence of stimulus (phantosmia); alteration in taste (parageusia); and loss of taste (dysgeustia); encephalitis. The cognitive dysfunction may be associated with, caused by, or based on a neurodegenerative condition characterized by excess CNS QUIN formation as described above. In a further aspect, the disclosure provides a compound for use in treating a cognitive dysfunction experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described above, wherein the compound has neurotrophic activity. The disclosure extends to a pharmaceutical composition containing said compound in an amount effective for reducing the symptoms of said cognitive dysfunction experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described above, for use in a method of treating or preventing said cognitive dysfunction. The disclosure extends to the use of a compound having neurotrophic activity for the treatment or prevention of a cognitive dysfunction experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described above. The disclosure extends to a compound having neurotrophic activity for use in the manufacture of a medicament for the treatment or prevention of a cognitive dysfunction experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described above. The disclosure extends to a pharmaceutical composition containing said compound in an amount effective for reducing the symptoms of said neurological manifestation experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described above, for use in a method of treating or preventing said cognitive dysfunction. The disclosure extends to the use of a compound having neurotrophic activity for the treatment or prevention of a neurological manifestation experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described above. The disclosure extends to a compound having neurotrophic activity for use in the manufacture of a medicament for the treatment or prevention of a neurological manifestation experienced by a patient secondary to a condition characterized by excess CNS QUIN formation as described. A further aspect of the disclosure provides a preventive or therapeutic pharmaceutical agent for at least one condition selected from the group consisting of neurological diseases, neuroinflammatory diseases, cognitive dysfunctions, and neurological manifestations secondary to an illness caused by a condition characterized by excess CNS QUIN formation as described above, said pharmaceutical agent comprising, as an active ingredient, a compound having neurotrophic activity. The compound may be as described above. The disclosure extends to a pharmaceutical composition containing a compound or pharmaceutical agent, as described above, for treatment and prevention of at least one of the abovementioned conditions, effects, and neurological manifestations referred to above. The composition may be formulated for administration to a patient in a delivery system or mode selected from the group consisting of solid dosage forms, tablets (including coated tablets, buccal tablets, and sublingual tablets), troches, capsules, powders, nasal or oral transmucosal administration agents (including powders, drops, sprays, aerosols, sublingual wafers, and the like), rectal suppositories, rectal creams, liquids, suspensions, emulsions, sterile solutions, topical compositions, inhalable compositions, transdermal patches (including microneedle systems), liniments, gels, or the like, and injections (intravenous, intramuscular, subcutaneous or otherwise). The composition may be formulated to deliver the active compound in a slow or extended release (ER) formulation. The ER formulation may comprise a sustained release (SR) or controlled release (CR) formulation. The compound may be provided as an ER, SR, or CR tablet or coated tablet. The compound may be provided as an ER, SR, or CR rectal suppository. The disclosure extends to a delivery system for the active compound, comprising a controlled-release or slow-release tablet. The disclosure extends to a delivery system for the active compound, comprising a controlled-release or slow-release transdermal (including microneedle) patch system. The disclosure extends to a delivery system for the active compound, comprising a controlled-release or slow-release rectal suppository preparation. The disclosure extends to a delivery system for the active compound, comprising a controlled-release or slow-release transmucosal preparation, including but not limited to a sublingual or buccal tablet or wafer. The delivery system may have pharmacokinetic characteristics suitable to limit the time to peak plasma and brain levels of the active compound, for mitigating harmful or unwanted side effects of the active compound in a patient. Aspects of the disclosure may also provide a method for treating or preventing a neurological condition due to excess QUIN and one or more adverse health conditions associated with a neurological condition due to excess QUIN, the method comprising a step of administering to a human or animal in need thereof a therapeutically effective amount of a compound having neurotrophic activity. The method may comprise a step of testing a human or animal to determine whether said human or animal has a neurological condition due to excess QUIN prior to performing the administering step. Aspects of the disclosure may also provide a method for treating or preventing a neurological condition due to excess QUIN and one or more adverse health conditions associated with a neurological condition due to excess QUIN, which comprises a step of administering to a patient who has been identified as having a neurological condition due to excess QUIN a therapeutically effective amount of a compound having neurotrophic activity. The method may further comprise a step of testing patients to identify a patient having a neurological condition due to excess QUIN. Aspects of the disclosure may also provide a method for treating or preventing a neurological condition due to excess QUIN and one or more health conditions associated with a neurological condition due to excess QUIN, the method comprising a step of selecting a patient who has a neurological condition due to excess QUIN and administering to said selected patient a therapeutically effective amount of a compound having neurotrophic activity. The method may further comprise a step of testing a patient to determine whether the patient has a neurological condition due to excess QUIN. The disclosed methods of treatment may comprise administering at least one tablet as described above in a treatment regime extending over the course of five to ninety days, e.g., over the course of one week to three months. The disclosed methods of treatment may comprise administering at least one rectal suppository as described above in a treatment regime extending over the course of five to ninety days, e.g., over the course of one week to three months. It will be appreciated, however, that treatment regimes having longer durations, e.g. three years, also fall within the scope of the invention. The disclosed methods of treatment may comprise administering the active compound parenterally in a dose of about 0.01 to 1000 mg / person / day, preferably 0.1 to 500 mg / person / day. The disclosed methods of treatment may comprise administering the active compound orally in a dose of about 0.01 to 500 mg / person / day, preferably 0.1 to 100 mg / person / day. In each of the aspects of the technology described herein, the compound having neurotrophic activity may be represented by the following formula: [CHEM. 1] wherein: X is independently selected from the group consisting of a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted aryl; and Ri is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted aryl; or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of the compound of formula CHEM 1 or any one of its enantiomers. The halogen atom may be selected from the group consisting of H, F, Cl, Br, and I. The compound may be selected from the group consisting of ketamine, (R)-ketamine, R(-)-ketamine, (S)-ketamine, and S(+)-ketamine. Ketamine, typically available as ketamine hydrochloride, is a racemic mixture containing S(+)-ketamine and R(-)-ketamine. Both enantiomers and metabolites differ in their pharmacokinetics and pharmacodynamics (such as molecular site of action). Therapeutically, ketamine is used as an anaesthetic, analgesic for acute and chronic (cancer and non-cancer) pain, and since a few years ago, as an antidepressant in treatment-resistant major depressive disorder and bipolar disorder. The daily dosage of ketamine differs depending on the condition and weight of the patient, the type of compound, the administration route, and the like. Ketamine may be safely used because it has few side effects. Since 2000, both the racemic mixture (Ketalar® or RS-ketamine) and the S(+)-ketamine enantiomer (Ketanest®, Spravato® or esketamine) are commercially available. Additionally, ketamine has several active metabolites. Major metabolites include norketamine (NK), comprising of (R)-norketamine and (S)-norketamine, (R)-dehydronorketamine, (S)-dehydronorketamine and hydroxynorketamine (HNK), of which multiple enantiomers are produced in the liver. (2R,6R)-HNK is the most studied ketamine metabolite due to its specific pharmacodynamic properties. About 20% of an oral dose of ketamine reaches the brain as ketamine, while the rest is metabolised and thus exerts its effects via the metabolites. It will be appreciated that metabolites may be identified which could be used on their own to treat depression or other neurological conditions as described herein (including long COVID), thereby avoiding the psychotropic effects of the ketamine. Such metabolites also fall within the scope of the presently disclosed technology. In one embodiment, the compound having neurotrophic activity may comprise (R)-ketamine, represented by the following formula: [CHEM. 2] or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug thereof. The primary metabolite may be selected from the group consisting of (R)-norketamine, (2R,6R)-hydroxynorketamine, (R)-dehydronorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine and (S)-dehydronorketamine. Clinical trials of slow release oral ketamine tablets for the treatment of depression have been promising and a new off-label application for a drug formulation that is already in development may be advantageous. Instead of the compounds discussed above, the compound in each parallel aspect of the present disclosure (or subset of claims) may comprise a serotonergic psychedelic, also referred to as a serotonergic hallucinogen, or other compound having a high affinity for serotonin (5-HT) receptors. The serotonergic psychedelic may be selected from the group consisting of psilocybin, LSD, / V, / V-Dimethyltryptamine (DMT), 5-methoxy- / V, / V-dimethyltryptamine (5-MeO-DMT), 2,5-Dimethoxy-4-iodoamphetamine (DOI), or an enantiomer of any one of these compounds, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of any one of these compounds or its enantiomers. Instead, the compound in each aspect of the technology may comprise noribogaine. The neurotrophic compound may comprise tabernanthalog. Microdosing The active compound, or each active compound in the case of compositions that include more than one such compound, may be delivered to the human or animal subject in a series of microdoses. It will be appreciated that the amount of a given compound that constitutes a microdose will depend on the type of compound and other factors described more fully below. Typically, a microdose comprises a small fraction of the “usually effective” or pharmacologically active dose of that compound. In the context of combinations (ensembles) of compounds for treatment, the use of microdosing can promote the safety of such combinations. As an example of possible microdosage amounts, and without limiting the generality of the available ranges, each of the microdoses of the active compound (or of each active compound in a combination) may comprise a dose in a range between 0% and 15% of a pharmacologically active dose of the compound. Each microdose may, for example, comprise about 10% of the pharmacologically active dose of the compound. The microdosing regimen may comprise administering or delivering a microdose of the active compound, (or of each active active compound in a combined composition), to the subject in an amount ranging from about 0.01 to 15,000 pg / person / day for a 70 kg individual. In certain embodiments, the microdose of each active compound may be administered in an amount ranging from about 0.01 to 3000 pg / person / day. In certain embodiments, the microdose of each active compound may be administered in an amount ranging from about 0.01 to 200 pg / person / day. The microdosing regimen may comprise administering the microdose orally, rectally or parenterally. In the case of psilocybin, an exemplary embodiment of the microdosing regimen may comprise administering the psilocybin to the subject in a dose of about 10 to 40 pg / kg / day, or approximately 1 to 3 mg per 70 kg individual per day. In the case of psilocin, an exemplary embodiment of the microdosing regimen may comprise administering the psilocin to the subject in a dose of about 10 to 30 pg / kg / day, or approximately 0.7 to 2.1 mg per 70 kg individual per day. In the case of LSD, an exemplary embodiment of the microdosing regimen may comprise administering the LSD to the subject in a dose of about 0.07 to 0.36 pg / kg / day, or approximately 5 to 25 pg per 70 kg individual per day. The microdosing regimen may comprise administering a plurality of microdoses of each compound (or each of the combination of compounds) to the subject at periodic intervals according to a dosing schedule. The dosing schedule may comprise administering the microdoses to the subject at intervals over the course of at least one prolonged treatment period. The prolonged treatment period may have a duration of at least seven days. However, to allow for neural growth according to the mechanism of action postulated for the disclosed treatment regimens, at least a month of treatment is likely to be required. In some cases, the duration of the treatment period may need to be significantly longer. The duration of the treatment period may accordingly range from one month to three years. The dosing schedule may comprise consecutive daily doses administered on Mondays and Tuesdays and then on Thursdays and Fridays, with no doses administered on Wednesdays, Saturdays and Sundays. This schedule may be expected to limit downregulation of receptors and provide a practical, easy to use regimen which may have a high compliance rate. It will be appreciated that other dosing schedules also fall within the scope of the disclosed technology. For example, the dosing schedule may comprise two consecutive dosing days followed by two non-dosing days. The dosing schedule may instead comprise “weekday” dosing, namely from Monday to Friday and not dosing on Saturday and Sunday. The dosing schedule may involve microdosing the subject every other day. Other dosing schedules are feasible, but may have shortcomings. For example, a regimen of one day on and two days off would inhibit downregulation but requires more compliance from patients than a simple regimen based on the days of the week. A further possible schedule would involve four days on and three days off, but once again may cause difficulties with compliance. By way of comparison, scheduling of microdosing among recreational drug users varies. The most popular dosing schedule involves two consecutive dosing days followed by two non-dosing days. Another popular approach involves “weekday” dosing, namely from Monday to Friday and not dosing on Saturday and Sunday. Additionally, some users follow a balanced approach, which involved dosing every other day. The dosage regimens and dosing schedules disclosed herein may be adjusted depending on the required amount, the treatment method, the adverse health condition, disorder, disease or neurological manifestation being treated, and the degree of need for each individual subject, amongst other relevant factors. The dosage may be determined depending specifically with reference to the age, the body weight, the general health state, the gender, the diet, the administration time, the administration method, the excretion rate, the drug combination, the medical condition of the patient, and the like. When administered to a patient having a cognitive dysfunction secondary to increased QUIN, the active compound may be delivered to the patient in an amount effective to reduce a symptom of cognitive dysfunction. The symptom of the cognitive dysfunction may comprise a loss of neurons. The compound may accordingly comprise psilocybin, represented by the following formula: [CHEM. 3] H or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of the compound of formula CHEM 3 or any one of its enantiomers. Instead, the compound may comprise psilocin or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of psilocin or any one of its enantiomers. Instead, the compound may comprise lysergic acid diethylamide (LSD) or an enantiomer thereof. Instead, the compound may comprise / V, / V-Dimethyltryptamine (DMT). Instead, the compound may comprise 5-methoxy- / V, / \ / -dimethyltryptamine (5-MeO-DMT) or an enantiomer thereof. Instead, the compound may comprise 2,5-Dimethoxy-4-iodoamphetamine (DOI) or an enantiomer thereof. Instead, the neurotrophic compound may comprise a psychoactive indole alkaloid. The compound may comprise ibogaine or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of ibogaine or any one of its enantiomers. The primary metabolite may comprise noribogaine. The neurotrophic compound may comprise tabernanthalog. The methods of treatment may include administering the active compound to a patient in need thereof. The patient may be a mammal. The patient may be a human. Delivery Systems and Modes The active compounds may be administered by using oral, nasal, rectal, transmucosal, transdermal, parenteral, intravenous, intramuscular, or subcutaneous modes of delivery, amongst others. The preferred modes of delivery are by oral, rectal, transmucosal and transdermal (including microneedle) administration. For oral administration, known dosage forms such as tablets, capsules, coated tablets, troches, or liquids such as solutions or suspensions may be used. Rectal administration may be performed using suppositories, creams, or the like. Oral transmucosal administration may be performed using buccal tablets or sublingual wafers, powders, drops, sprays, aerosols, or the like. Nasal transmucosal administration may be performed using powders, drops, sprays, aerosols, or the like. Transdermal administration may be performed using patches, liniments, gels, or the like. Parenteral administration may be performed by intravenous, intramuscular, or subcutaneous injection. The pharmaceutical composition according to the present disclosure may contain, in addition to the disclosed active compound, another medical ingredient or a pharmacologically acceptable salt thereof. The pharmaceutical composition may contain one or more suitable pharmacologically acceptable carrier substances, depending on the administration form or delivery system. The pharmacologically acceptable carrier substance is not particularly limited. Examples include an antioxidant, a stabilizer, a preservative, a flavouring agent, a colouring agent, a solubilizer, a solubilizing agent, a surfactant, an emulsifier, a defoamer, a viscosity adjuster, a gelling agent, an absorption enhancer, a dispersant, an excipient, a pH adjuster, a carrier agent and the like. In some of the described compositions and delivery systems, the carrier may comprise dimethyl sulfoxide (DMSO). For delivery systems which are prepared as a formulation for oral administration, a slow, sustained, controlled or extended release (ER) oral dosage form such as a tablet or capsule may be preferable; and for those prepared as a formulation for rectal administration, a semi-solid formulation such as a cream or a suppository may be preferable; and for those prepared as a formulation for nasal or oral transmucosal administration, a formulation with the form of a sublingual wafer, buccal tablet, or powder may be preferable; and for those prepared as drops, an aerosol agent may be preferable; and for those prepared as a formulation for injection, a solution or suspension may be preferable. Any of these formulations may be prepared by any method known to those skilled in the pharmaceutical arts, for example, the methods described in Remington’s Pharmaceutical Sciences. For the formulation for injection, as examples of the carrier, plasma-derived proteins such as albumin, amino acids such as glycine, and sugars such as mannitol, may be used, and furthermore, buffers, solubilizing aid, isotonic agents, and the like may be used. In addition, when it is used as a water-soluble formulation or a freeze-dried formulation, for example, surfactants such as Tween® 80 and Tween® 20 may be used to inhibit aggregation. For the formulation for parenteral administration other than the formulation for injection, as examples of the carrier, distilled water or physiological saline, a polyalkylene glycol such as polyethylene glycol, oils of vegetable origin, hydrogenated naphthalene, and the like may be used. For example, the formulation for rectal administration such as a suppository may use, as excipients, for example, a polyalkylene glycol, vaseline, cacao oil, and the like. For the formulation for vaginal administration, as examples of the carrier, absorption enhancers such as bile salts, ethylenediamine salts, and citrates may be used. The formulations for inhalation may be solid. Excipients such as lactose may be used. The drops for nasal administration may comprise water or oil solutions. The formulations for transdermal administration may comprise a carrier such as DMSO, or any other agent may be used. The dosage and administration plans may be adjusted depending on the required amount, the treatment method, the disorder or adverse health condition being treated, the degree of need, and the like for each individual subject. The dosage may be determined depending specifically with reference to the age, the body weight, the general health state, the gender, the diet, the administration time, the administration method, the excretion rate, the drug combination, the medical condition of the patient, and the like. When administered to a patient having a cognitive dysfunction due to the long-term effects of neurological condition due to excess QUIN, the active compounds may be contained in an amount effective to reduce the symptom of cognitive dysfunction. The symptom of the cognitive dysfunction may comprise a loss of neurons. Mechanisms of Action It is postulated that the beneficial effects of ketamine on the prevention and treatment of neurological conditions associated with increased QUIN may be mediated by antagonism of QUIN neurotoxic effects and by induction of an increase of brain-derived neurotrophic factor (BNDF) and subsequent binding of BDNF to the neurotrophic tyrosine kinase receptor B (TrkB). Ketamine and (2R,6R)-HNK also act directly on TrkB, leading to secondary intracellular processes and enhancing synaptic plasticity and neuroplasticity. It is postulated that the exceptional ability of ketamine in the current setting, e.g. for the prevention and treatment of neurological conditions including long COVID, lies in the fact that it both blocks the effects of QUIN (especially overstimulation of NMDA receptors and potentiation of glutamate signalling at these receptors) as well as damping its production, and then subsequently effecting neural growth and synaptoplasticity via a second mechanism through BDNF. In more detail, ketamine is exceptional in the sense that it both counteracts the effect of QUIN neurotoxicity by blocking the NMDA receptor, thus preventing QUIN-induced excitotoxicity and excess glutamatergic excitotoxicity, as well as having neurotrophic and synaptogenic effects via its action on TrkB receptors as well as its secondary effect on glutamate release secondary to blocking NMDA receptors on inhibitory interneurons and thus effecting AMPA receptor activation and subsequent increases in BDNF. In addition, Ketamine inhibits nuclear factor Kappa B (NF-kB) transcription factor, thereby decreasing indoleamine 2,3-dioxygenase (IDO) expression and thereby decreasing activation of the kynurenine (KYN) pathway of Trp degradation and QUIN formation. Decreased activation of NF-kB also leads to decreased levels of pro-inflammatory cytokines in the brain. Ketamine, through its metabolites (R)-HNK and dehydronorketamine, acts as an antagonist and negative allosteric modulator at the alpha-7 nicotinic receptor (a7nAChR) thereby modulating its effects and decreasing neuroinflammation. Ketamine increases formation of kynurenic acid (KYNA), which acts as a neuroprotective KYN metabolite at low concentrations. The beneficial effects of Ketamine on the gut microbiome contribute to downregulation of the inflammatory response, further contributing to decreased QUIN formation. The Kynurenine pathway of Tryptophan degradation and Quinolinic acid neurotoxicity Trp is an essential amino acid. It is metabolised via the methoxyindole pathway (5%), through which 5-hydroxytyptamine / serotonin (5HT) and melatonin is formed, or the KYN pathway (95%), leading to the formation of various intermediate metabolites and eventually to the formation of NAD+ via degradation of QUIN. Some of the intermediate metabolites in the KYN pathway have either neuroprotective or neurotoxic effects. Several enzymes in the KYN pathway are induced or inhibited in disease processes, leading to alterations in the formation of KYN pathway metabolites. Scheme 1 (below) outlines the substrates, intermediate metabolites and enzymes in the degradation pathways of Trp. Kynurenic acid (KA) is a neuroprotective metabolite in low concentrations, while QUIN, 3-hydroxykynurenine (3-HK) and 3-hydroxy-anthranilic acid (3-HAA) are neurotoxic at high concentrations. 5-HTP Tryptophan Serotonin Formyl ky nu ren the Kynurenine (KAT's Melatonin KA AA 3-HAAO 3-HK uren inose' 3-HAA ACMS Non-enzymic AMS XA PA QUIN CQP / ?TJ) NA MN NAAD NAD+ SCHEME 1 Tryptophan is metabolized via different pathways. The methoxyindole pathway (5%) forms 5-5 hydroxytyptamine / serotonin (5HT) and melatonin. The kynurenine pathway leads to formation of Formylkynurenine via the action of Indoleamine dioxygenase 1 and 2 ((IDO-1) and (IDO-2)) in brain tissue and other tissues, as well as tryptophan dioxygenase (TDO) in the liver. Formylkynurenine is metabolized by N-Formylkynurenine foramidase to kynurenine (KYN). KYN is subsequently metabolized to kynurenic acid (KYNA) by kynurenine aminotransferases (KAT’s), 10 to anthranilic acid (AA) by kynureninase or to 3-hydroxykynurenine (3-HK) by kynurenine monooxygenase (KMO). AA can undergo non-specific hydroxylation to form 3-hydroxy anthranilic acid. 3-HK can be metabolized to xanthurenic acid (XA) by KAT or, preferentially to 3-hydroxy anthranilic acid (3-HAA) by kynureninase (L-Kynurenine hydrolase). 3-HAA is metabolized to 2-amino-3-carboxymuconic acid-6-semialdehyde (ACMS) by 3-hydroxyanthranilic acid 3,4-15 dioxygenase (3-HAAO). A small portion of ACMS can be metabolized to picolinic acid (PA) by spontaneous nonenzymic cyclization after formation of 2-aminomuconic acid-6-semialdehyde (AMS) by ACMS decarboxylase, but the majority of ACMS is metabolized to quinolinic acid (QUIN) by nonenzymic cyclization. QUIN is metabolized by quinolinic acid phosphoribosyltransferase (QPRT) to nicotinic acid mononucleotide (NAMN) and subsequently to nicotinic acid dinucleotide (NAAD) and then to nicotinamide adenine dinucleotide (NAD+). Importantly, both 3-HK and AA can convert to 3-HAA, which converts to the neurotoxic metabolite QUIN via the unstable intermediate product ACMS. Adapted from Badawy AA. Tryptophan metabolism and disposition in cancer biology and immunotherapy. Biosci Rep. 2022 Nov 30;42(11):BSR20221682. doi: 10.1042 / BSR20221682. PMID: 36286592; PMCID: PMC9653095. In extra-neural tissue, mainly liver and lung, Trp is metabolised via tryptophan-2,3-dioxygenase (TDO). In the brain, and to a lesser extent in lung tissue, lndoleamine-2,3-dioxygenase 1 (IDO1) and lndoleamine-2,3-dioxygenase 2 (IDO2) metabolize Trp. The majority of Trp is metabolized outside the brain, but during disease states the blood-brain barrier can be disrupted, causing peripheral metabolites of the KYN metabolic pathway to cross into the brain. Under such circumstances peripheral metabolites are formed via increased function of TDO. The first metabolite in the KYN pathway is N-formylkynurenine, which is hydrolysed by kynurenine foramidase to KYN. Subsequently KYN can be hydroxylated to 3-HK by kynurenine monooxygenase (KMO), followed by hydrolysis to 3-hydroxyanthranilic acid (3-HAA) by kynureninase. Kynureninase can also hydrolyse KYN to anthranilic acid (AA). KYN can also be metabolized to kynurenic acid (KA) by kynurenine aminotransferase l-lV (KAT). A small portion of 3-HK is metabolized to xanthurenic acid (XA) by KAT’s. However, the majority of 3-HK is hydrolysed to 3-HAA, which is metabolized by the most active enzyme in the KYN pathway, 3-hydroxyanthranilic acid 3,4-dioxygenase (3-HAAO), to form the unstable intermediary 2-amino-3-carboxymuconic acid semialdehyde (ACMS). This is of central importance in the KYN pathway, as the major flux of the metabolic pathway shunts ACMS towards QUIN via nonenzymic spontaneous cyclization. This is spontaneous process is central to the accumulation of QUIN in disease states. The alternative reaction is decarboxylation of ACMS to form 6-aminomuconic semialdehyde by 2-amino-3-carboxymuconic acid semialdehyde decarboxylase (ACMSD) and then picolinic acid (PA) via non-enzymatic cyclization. However, the decarboxylation enzyme ACMSD is present at very low levels in the brain and is inhibited by QUIN. Initiation of the inflammatory cytokine cascade after tissue injury or infection activates gene expression of enzymes in the KYN pathway and enhances their function. TDO is stimulated by cortisol, which can be elevated in disease and stress states via the hypothalamic-pituitary-adrenal axis (HPA). IDO-1 and IDO-2 are induced by cytokines, notably Interferons, especially Interferon-Y (IFN-Y), Tumor necrosis factor a (TNFa) as well as Interleukin- 6 (IL-6). IL-6 is produced by macrophages, neutrophils, dendritic cells, T- and B-lymphocytes, endothelial cells, microglia and neurons in response to activation during inflammation. In addition, IFN-Y activates kynurenine 3-monooxygenase (KMO). KMO activity regulates the levels of KYN, thereby influencing the rate of formation of KYNA. Shunting KYN metabolism away from KYNA production reduces levels of neuroprotective KYNA. KYN and 3-HK formed by increased systemic production readily cross the blood-brain barrier and is available in the central nervous system (CNS) for metabolism via the KYN pathway. KMO is not saturated under physiological conditions, therefore any increase in brain KYN will lead to increased production of 3-HK and subsequently to increases in QUIN. QUIN inhibits the kynurenine transaminases enzymes (KAT l-IV), thereby decreasing neuroprotective KYNA formation. During disease states, disruption of the blood-brain barrier allows peripheral QUIN, which does not normally cross the blood-brain barrier, to enter the CNS. Disruption of the bloodbrain barrier also allows entry of macrophages into the CNS. Macrophages can produce 20- to 30-fold more QUIN than microglia. Increased activity of TDO and IDO1 and IDO2 increase flux of Trp down the KYN pathway, thereby increasing levels of QUIN severalfold. Iron (Fe+) is a co-factor of 3-hydroxyanthranilic acid oxygenase (3-HAAO). Neuronal damage causes increased brain Fe+, thereby stimulating the activity of 3-HAAO, leading to formation of ACMS, the QUIN precursor, thereby further increasing production of QUIN. The metabolic reactions of metabolites in the KYN pathway are enhanced and controlled by several enzymes, which are enhanced during inflammatory conditions. Negative feedback, substrate inhibition and other control mechanisms are involved in these processes. However, the exception to this is the formation QUIN, which forms spontaneously via nonenzymatic cyclisation from the unstable intermediate molecule ACMS. There is no natural mechanism whereby excessive QUIN formation is prevented in the presence of excess ACMS. ACMS can, to a limited extent, be converted to picolinic acid (PA) via an unstable intermediate by the enzyme aminocarboxymuconate-semialdehyde decarboxylase (ACMSD). ACMSD exists in two forms. ACMSD1 is present in the liver and kidney, and at low levels in brain tissue, while ACMSD2 is found only in the liver and kidney. Excessive QUIN inhibits ACMSD1 in the brain, leading to further increases in QUIN. The rate-limiting enzyme, quinolinate phosphoribosyltransferase (QPRT), converts QUIN into nicotinic acid mononucleotide (NAMN) in astrocytes and neurons, which is subsequently converted to NAD+. QUIN metabolism by QPRT is rapidly saturated. QPRT is inhibited by high levels of QUIN. There are also far fewer cells containing QPRT compared to 3-HAAO in the brain. Circumstances leading to high levels of QUIN can therefore set up a vicious cycle in which ever increasing QUIN levels cause neuronal and astrocyte damage, while simultaneously inhibiting breakdown of QUIN. QUIN neurotoxicity occurs through several mechanisms. It potentiates its own excitotoxicity as well as that of glutamate (GLU). QUIN is approximately as active as GLU at stimulating the NMDA receptor. It acts selectively at NMDA receptor subtypes with NR2A and NR2B subunits, leading to massive Calcium influx and excitotoxicity. QUIN additionally increases GLU excitotoxicity at NMDA receptors. QUIN stimulates GLU release, inhibits uptake of GLU by astrocytes by inhibiting amino acid transporter systems and inhibits glutamine synthetase activity, thus limiting recycling of GLU to glutamine. Additional mechanisms of neurotoxicity include increased tau phosphorylation due to decreased expression of tau phosphatases, impairment of sarco / endoplasmic reticulum Ca2+-ATPase (SERCA) pump activity via NMDA receptor stimulation and disruption of the neuronal and astrocyte cytoskeleton via increases in intermediate filament hyperphosphorylation via NMDA channel Calcium influx. NMDA receptor-independent mechanisms of QUIN neurotoxicity include lipid peroxidation via reactive oxygen species (ROS) generation and interference with energy production and mitochondrial function. In addition, QUIN excitotoxicity is increased by 3-HK and reactive oxygen radicals. QUIN induces increased expression of TNF-a and IL-6, thereby further enhancing its own synthesis via increases in metabolism in the KYN pathway via IDO enhancement. Gut microbiota play a major role in the metabolism of Trp metabolites. Nerve signaling via the vagus nerve, hormonal signaling via the HPA-axis and immune signaling via cytokines influence levels of circulating Trp and KYN pathway metabolites. Cytokines, neurotransmitters and neuropeptides are involved in regulation of Trp and KYN pathway metabolites. In addition, the integrity of the blood-brain barrier is influenced by products of the gut microbiota. Gut microbiota can synthesize Trp as well as metabolize it to generate kynurenines, serotonin, tryptamine and indole derivatives. The indole derivatives and KYN produced by the microbiota interact with the aryl hydrocarbon receptors on immune cells. Gut microbiota can synthesize QUIN and generate IDO-1 which induces QUIN and KYNA production in gut mucosal cells and immune cells. Under normal physiological conditions QUIN concentrations are maintained at levels which do not cause widespread excitotoxicity. These levels increase thousandfold to micromolar levels during inflammation, causing extensive and rapid neurotoxicity. Calcium influx activates proteases and endonucleases, leads to generation of reactive oxygen radicals and nitric oxide and eventually cause apoptosis due to lipid peroxidation. Astrogliosis induced by QUIN leads to release of cytokines and inhibition of GLU uptake, further exacerbating NMDA receptor mediated excitotoxicity. Ketamine as NMDA receptor antagonist and QUIN blocker Ketamine was originally developed as an anaesthetic and analgesic drug. Subsequently Ketamine has been re-purposed for several neuro-psychiatric conditions. Ketamine is a noncompetitive direct antagonist at the NMDA receptor. Both (R-)-ketamine and (S+)-ketamine promote secondary glutamate release and agonism at a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors via NMDA blockade at inhibitory interneurons, with subsequent activation of mammalian target of rapamycin complex 1 (mTORCI), resulting in release of BDNF and activation of Tropomyosin receptor kinase B (TrkB) and the extracellular-signal-related kinase (ERK) and ultimately leads to synaptogenesis and repair of damaged brains via neurogenesis. S-Norketamine also independently activates mTORCI. In addition, Ketamine and (2R6R)-HNK interact directly with TrkB, facilitating its function. Ketamine has been proven in both experimental and clinical settings to counteract the neurotoxic effects of QUIN on neurons and astrocytes and production of QUIN by microglia. Its effects on microglial QUIN have been shown to serve as a marker of success in treating lipopolysaccharide induced depression in a pre-clinical model, as well as in humans with major depression in a small clinical study. Chronic inflammation causes microglial activation and leads to altered neurotransmission and neuronal damage. Ketamine increases brain levels of protective KYNA and elevates synaptic proteins, such as post-synaptic density protein 95, which are essential in the organization and clustering of neurotransmitter receptors at the post-synaptic membrane. Ketamine supresses platelet aggregation by various mechanisms, including a decrease in the release of platelet activating factor (PAF), alters the gut microbiome and promotes increases in beneficial gut microbes, inhibits IL-6 gene expression in activated macrophages and has antiinflammatory effects via its direct action on cytokine production Autophagy is a protein degradation pathway. Neurons have an extremely high protein turnover rate and when the autophagy process gets disrupted, it results in a build-up of toxic proteins, which leads to neurodegeneration. Apoptosis and autophagy interact with each other and jointly participate in the regulation of cell fate. Ketamine has been shown to protect astrocytes by alleviating apoptosis in an animal model. This disclosure proposes that ketamine, its enantiomers, and or its metabolites can similarly alleviate the neurological effects of disruption of autophagy. R(-)-ketamine has a better pharmacological profile than S(+)-ketamine and has lower potential for dependency with repeated use because its binding to the NMDA receptor complex is weaker. The (R)-ketamine may accordingly be preferable to the use of racemic ketamine or the S(+)-ketamine enantiomer for the disclosed treatment of excess QUIN. The metabolite (2R,6R)-HNK has a short half-life of approximately one hour but has shown persistent effects in the treatment of depression and neuropathic pain. However, unlike ketamine, (2R,6R)-HNK is not associated with motor incoordination and has a lower potential for abuse or addiction The neurotrophic effects of (2R,6R)-HNK are independent of the NMDA receptor but are related to agonistic activity at the AM PA receptor and TrkB activation. Psilocybin Psilocybin is a naturally occurring compound found in a group of polyphyletic mushrooms including the genus Psilocybe. Psilocybin is a prodrug metabolized through in vivo dephosphorylation to psilocin, which is presumed to be the active agent in the central nervous system. The behavioural effects of psilocin appear to be mediated primarily by agonist activity at the 5-hydroxytryptamine 2A (5-HT2A) receptor; however, 5-HT2A activity does not appear to account fully for its effects. Pre-clinical data suggests that psilocin interacts directly with TrkB, facilitating BDNF binding and thereby leading to synaptogenesis and neurogenesis. Psilocybin is characterized by low physiological toxicity and low abuse liability, as demonstrated by marginal levels of nonhuman drug self-administration. Psilocybin has shown highly promising results in the treatment of diverse conditions and preliminary data has shown promise for psilocybin in the treatment of anxiety, depression, addiction to smoking and alcoholism. It has been shown that a single dose of psilocybin given to mice prompted an immediate and long-lasting increase in connections between neurons. Although ketamine and serotonergic neurotrophic psychedelics like psilocybin have affinity for vastly different receptors (NMDA, 5-HT2A), they ultimately initiate similar plastic adaptations in the prefrontal cortex through the involvement of BDNF and TrkB. LSD, DMT, 5-MeO-DMT, DOI, Noribogaine, Tabemanthalog LSD, DMT, 5-MeO-DMT, DOI act as neurotrophic substances via stimulation of BDNF. Noribogaine and tabemanthalog act as a neurotrophic through a combination of increases in BDNF and increased expression of the glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor with neuroprotective effects. In addition, noribogaine is a weak NMDA receptor antagonist and a non-competitive inhibitor of substrate uptake by the serotonin transporter (SERT). The presently disclosed technology may include further aspects. For example, the technology may provide a substance for use in modifying the course and severity of a neurocognitive disorder, long-term adverse effect or sequela of activation of the kynurenine pathway, wherein the substance comprises a compound selected from the group consisting of ketamine, (R)-ketamine, (S)-ketamine, ketamine metabolites, (R)-norketamine, (2R,6R)-hydroxynorketamine, (R)-dehydronorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (S)-dehydronorketamine, and pharmaceutically acceptable salts thereof. The substance may be provided in a composition. The disclosed technology may further provide a method of modifying the course and severity of a neurocognitive disorder, or long-term adverse effect or sequela of activation of the kynurenine pathway, the method comprising administering a substance to a human or animal subject, wherein the substance comprises a compound selected from the group consisting of ketamine, (R)-ketamine, (S)-ketamine, ketamine metabolites, (R)-norketamine, (2R,6R)-hydroxynorketamine, (R)-dehydronorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (S)-dehydronorketamine and pharmaceutically acceptable salts thereof. The substance may be provided in a composition. The neurocognitive disorder, adverse effect or sequela may be associated with excess quinolinic acid concentration levels in the subject. The substance may counter, inhibit or suppress the effects of excess quinolinic acid (QUIN) concentration levels in the subject. The neurocognitive disorder may be a long-term neurocognitive disorder. The neurocognitive disorder may be associated with long COVID. The compound may be the sole active agent for treating said neurocognitive disorder, or it may be provided as an adjunctive to a second substance in the composition. The compound may be isolated from its enantiomer or synthesized de novo. The step of modifying the course and severity of the disorder may involve an action selected from the group consisting of: curing the neurocognitive disorder, preventing the neurocognitive disorder, reducing the severity of the neurocognitive disorder, reducing the incidence of the neurocognitive disorder, reducing the duration of the neurocognitive disorder, and any combination thereof. Treatment of the neurocognitive disorder using the disclosed compound or method may result in relief from the neurocognitive disorder, wherein the relief involves outcomes similar to the foregoing. Modifying the course and severity of the neurocognitive disorder, or administering the substance or composition, may be performed under conditions effective for the substance to bind to a receptor of the subject and cause relief to the subject. The modification or administration may be performed under conditions effective for an action at an ion channel, neurotransmitter systems, neurotransmitter pathway, or receptor selected from an ionotropic glutamate receptor, a 5-HT2A receptor, a 5-HT2B receptor, an opioid receptor, an acetylcholine receptor, a sigma 1 receptor, a K channel, a Na channel, and / or a Ca channel. The modification or administration may be performed under conditions effective for an action to counteract the effects of excessive levels of quinolinic acid in the brain. The modification or administration may be performed under conditions effective for an action to have neurotrophic effects. The modification or administration may be performed under conditions effective for an action to cause increased levels of BDNF or increased levels of GDNF. The modification or administration may be performed under conditions effective for an action at an ionotropic glutamate receptor, and wherein the ionotropic glutamate receptor is an NMDA receptor. The modification or administration may be performed under conditions effective for an action at an ionotropic glutamate receptor, and wherein the ionotropic glutamate receptor is an AM PA receptor. The action at the ionotropic glutamate receptor may comprise voltage dependent channel block of NMDA receptors expressed by the membrane of a cell. The action at the ionotropic glutamate receptor may comprise voltage dependent channel block of NMDA receptors expressed by the membrane of a cell with a preferential effect on NMDA receptors containing NR2A and NR2B subunits. The action at the ionotropic glutamate receptor may comprise induction of synthesis of synaptic proteins that contribute to neuronal plasticity and contribute to the membrane expression of said synaptic proteins. In certain embodiments, the compound may be ketamine. The ketamine may be provided in the form of a pharmaceutically acceptable salt. In the disclosed method, the ketamine may be delivered at a total daily dosage of 0.1 mg to 1,000 mg. The administration of the disclosed compound, substance or composition may modify the course and severity of the neurocognitive disorder by relieving the disorder in the subject. The relief may begin within six weeks after the initial administration. The disclosed compound, substance or composition may be administered via a route selected from the group consisting of: oral, intramuscular, intravenous, intraperitoneal, intranasal, subcutaneous, sublingual, intrathecal, transdermal, buccal, vaginal, rectal, topical, and any combination thereof. The administration may involve prolonged administration by a sustained release dosage form of ketamine, a prolonged administration time of ketamine, a repeated administration, or a combination thereof. The administration of the compound, substance or composition may be performed in addition to or in combination with the administration to the subject of one or more other neurotrophic medications. The substance may accordingly include at least one further compound or element having neurotrophic activity. The method or treatment may comprise administering a composition comprising (i) a combination of ketamine, (R)-ketamine, (S)-ketamine, ora pharmacologically acceptable salt, solvate, hydrate, primary metabolite or metabolite, or prodrug thereof, with (ii) one or more of a serotonergic psychedelic which may comprise psilocybin or an enantiomer thereof, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of psilocybin, or any of its enantiomers, or LSD or N,N-dimethyltryptamine (DMT) or 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) or an enantiomer thereof or 2,5-dimethoxy-4-iodoamphetamine (DOI) or an enantiomer thereof, to the subject. The method or treatment may comprise administering a composition comprising a combination of (i) ketamine, (R)-ketamine, (S)-ketamine, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite or metabolite, or prodrug thereof, with (ii) one or more neurotrophic compounds or enantiomers thereof, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite, or prodrug of noribogaine or tabernanthalog, to the subject. The method or treatment may comprise administering a composition comprising a combination of(i) ketamine, (R)-ketamine, (S)-ketamine, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite or metabolite, or prodrug thereof, with (ii) one or more of lithium, zinc, or magnesium, to the subject. The method or treatment may comprise administering a composition comprising a combination of (i) ketamine, (R)-ketamine, (S)-ketamine, or a pharmacologically acceptable salt, solvate, hydrate, primary metabolite or metabolite, or prodrug thereof, with (ii) one or more of imipramine or any of its enantiomers or metabolites or memantine or riluzole or lanicemine or rislenemdaz or esmethadone or minocycline or melatonin or butyrate or an anti-inflammatory agent or galantamine or naltrexone or naloxone, to the subject. The method or treatment may comprise administering the substance or composition according to an intermittent treatment schedule selected from every other day, once every three days, two days per week, three days per week, four days per week, five days per week, six days per week, once weekly, every other week, every other two weeks, one week per month, every other month, every other 2 months, every other three months, one week per year, and one month per year. The administration of the composition may be alternated with a placebo in the selected intermittent treatment schedule. Instead of or in addition to the placebo, the method may include administering one or more of lithium, zinc, or magnesium to the subject. The increased or excess quinolinic acid may be caused by a pathogen or trauma or physical treatment or medication or an autoimmune disease or a hazardous substance or brain hypoperfusion or body habitus. The trauma may be blunt trauma or penetrating trauma or a surgical procedure. The physical treatment may be radiation. The medication may be chemotherapy or immunotherapy. The autoimmune disease may be Crohn’s Disease or Ulcerative Colitis or inflammatory bowel disease or Behcet’s disease or systemic lupus erythematosus or rheumatoid arthritis or primary Sjogren’s syndrome or Celiac disease or autoimmune thyroiditis or Grave’s disease. The hazardous substance may be a chemical or a fume or a gas or a dust or a vapour or a nanoparticle. The brain hypoperfusion may be caused by a thrombus or a haemorrhage or cardiac arrest. The body habitus may be morbid obesity. The pathogen may be selected from the group consisting of a virus, a bacterium, a protozoan, a prion, a viroid, and a fungus. Sepsis may be caused by any of these pathogens and may contribute to the neurocognitive disorder. In specific embodiments, the pathogen may be a virus. The virus may be a coronavirus or SARS-CoV-2 or SARS-CoV-1 or MERS-CoV or Human immunodeficiency virus or Zika virus or Influenza virus or Highly Pathogenic Avian Influenza virus or Bovine Influenza virus or Epsteinn-Barr virus or Coxsackie virus or Hepatitus C virus. In specific embodiments, the pathogen may be a bacterium. The bacterium may be a Gram-negative bacterium or Borrelia burgdorferi or Mycobacterium tuberculosis or Streptococcus, or Staphylococcus or Listeria or Haemophilus or Neisseria or Pseudomonas or Escherichia. In specific embodiments, the pathogen may be a protozoan. The protozoan may be Amoeba or Entamoeba or Giardia or Rhizopoda or Acanthamoeba or Sarcodina or Plasmodium or Trypanosoma. In specific embodiments, the pathogen may be a fungus. The fungus may be Cryptococcus or Aspergillus or Histoplasma or Candida or Pneumocystis or Blastomyces or Mucorales or Zygomycota or Paracoccidioides. The subject may be a vertebrate. The vertebrate may be human. The foregoing description has been presented for the purpose of illustration; it is not intended to be exhaustive or to limit the technology to the precise forms disclosed. Persons skilled in the relevant art can appreciate that many modifications and variations are possible in light of the above disclosure. The language used in the specification has been principally selected for readability and instructional purposes, and it may not have been selected to delineate or circumscribe the inventive subject matter. It is therefore intended that the scope of the present disclosure be limited not by this detailed description, but rather by any claims that issue on an application based hereon. Accordingly, the present disclosure is intended to be illustrative, but not limiting, of the scope of any accompanying claims. Finally, throughout the specification and claims, unless the context requires otherwise: • “comprise” or variations such as “comprises” or “comprising” will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers; • “excess” and variations such as “excessive”, when used in the context of QUIN formation or concentration, will have the meaning defined in the Summary section of this disclosure; • “Long COVID” will be understood to mean the syndrome referred to as Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), also known as long COVID syndrome, long COVID-19 syndrome, post-COVID-19 syndrome, COVID long-haul syndrome, or long-tail COVID; “neurological condition” will be understood to encompass one or more conditions selected from the group consisting of cognitive decline, cognitive impairment; decline or deficits in memory, including declarative memory, working memory, and long-term memory; decline or deficits in processing speed and executive function; declines or deficits in perceptual motor control, learning, decision making, planning, social cognition, self-awareness, attention and complex attention; “brain fog” and fatigue; • “treatment” and variations such as “treating” will be understood to encompass treatment, reduction in severity of, reduction in incidence of, and reduction in duration of the condition, disorder, effect or sequela concerned; • the term “prevention” and variations such as “preventing” will be understood to encompass prevention and prophylaxis; and • the phrase “treatment or prevention” shall be understood to encompass either or both treatment and prevention. REFERENCES Badawy AA. Tryptophan metabolism and disposition in cancer biology and immunotherapy. Biosci Rep. 2022 Nov 30;42(11):BSR20221682. doi: 10.1042 / BSR20221682. PMID: 36286592; PMCID: PMC9653095 Guillemin GJ. Quinolinic acid, the inescapable neurotoxin. FEBS J. 2012 Apr;279(8): 1356-65. doi: 10.1111 / j.1742-4658.2012.08485.x. Epub 2012 Mar 27. PMID: 22248144. Lawler NG, Gray N, Kimhofer T, Boughton B, Gay M, Yang R, Morillon AC, Chin ST, Ryan M, Begum S, Bong SH, Coudert JD, Edgar D, Raby E, Pettersson S, Richards T, Holmes E, Whiley L, Nicholson JK. Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses. J Proteome Res. 2021 May 7;20(5):2796-2811. doi: 10.1021 / acs.jproteome.1c00052. Epub 2021 Mar 16. PMID: 33724837. Ly C, Greb AC, Cameron LP, Wong JM, Barragan EV, Wilson PC, Burbach KF, Soltanzadeh Zarandi S, Sood A, Paddy MR, Duim WC, Dennis MY, McAllister AK, Ori-McKenney KM, Gray JA, Olson DE. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018 Jun 12;23(11):3170-3182. doi: 10.1016 / j.celrep.2018.05.022. PMID: 29898390; PMCID: PMC6082376. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari Tl. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016 Sep;55(9):1059-77. doi: 10.1007 / s40262-016-0383-6. PMID: 27028535. Verdonk F, Petit AC, Abdel-Ahad P, Vinckier F, Jouvion G, de Maricourt P, De Medeiros GF, Danckaert A, Van Steenwinckel J, Blatzer M, Maignan A, Langeron O, Sharshar T, Callebert J, Launay JM, Chretien F, Gaillard R. Microglial production of quinolinic acid as a target and a biomarker of the antidepressant effect of ketamine. Brain Behav Immun. 2019 Oct;81:361-373. 5 doi: 10.1016 / j.bbi.2019.06.033. Epub 2019 Jun 28. PMID: 31255681. Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10 10.1124 / pr.117.015198. Erratum in: Pharmacol Rev. 2018 Oct;70(4):879. doi: 10.1124 / pr.116.015198err. PMID: 29945898; PMCID: PMC6020109.

Claims

1. A compound for use in the treatment or prevention of at least one long-term effect of a neurological condition in a human or animal subject, the long-term effect having persisted in the subject for longer than 28 days, wherein said compound has neurotrophic activity and is preselected for its effectiveness to counter, inhibit or suppress excess central nervous system (CNS) quinolinic acid (QUIN) concentration levels in the subject.

2. The compound for use as claimed in claim 1, wherein the neurological condition is associated with activation of the kynurenine pathway in the subject.

3. The compound for use as claimed in claim 1 or claim 2, wherein the neurological condition is associated with long COVID.

4. The compound for use as claimed in any one of claims 1 to 3, which is preselected for its effectiveness to counter, inhibit or suppress QUIN concentration levels above about 40 nM in cerebrospinal fluid of the subject.

5. The compound for use as claimed in any one of claims 1 to 4, which is selected from the group consisting of ketamine, (R)-ketamine, (S)-ketamine, (R)-norketamine, (2R,6R)-hydroxynorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (R)-dehydronorketamine, (S)-dehydronorketamine and pharmaceutically acceptable salts thereof.

6. The compound for use as claimed in any one of claims 1 to 4, wherein the compound is represented by the following formula:[CHEM. 1]wherein:X is independently selected from the group consisting of a halogen atom, optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted aryl; andRi is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, and optionally substituted aryl;or an enantiomer thereof; or a pharmacologically acceptable salt, solvate or hydrate of the compound of formula CHEM 1 or any one of its enantiomers.

7. The compound for use as claimed in claim 5 or claim 6, wherein the compound comprises (R)-ketamine, or a pharmacologically acceptable salt, solvate, or hydrate thereof.

8. The compound for use as claimed in any one of claims 1 to 4, wherein the compound is psilocybin or an enantiomer thereof; or a pharmacologically acceptable salt, solvate, or hydrate thereof.

9. A pharmaceutical composition comprising the compound for use as claimed in any one of claims 1 to 8, and at least one other compound or element having neurotrophic activity.

10. The pharmaceutical composition as claimed in claim 9, which comprises any one of the following compounds (i) to (iii) in combination with at least one of the following compounds (iv) to (xxiv) or pharmacologically acceptable enantiomers, salts, solvates or hydrates thereof:i. ketamine, (R)-ketamine, R(-)-ketamine, (S)-ketamine, or S(+)-ketamine;ii. (R)-norketamine, (2R,6R)-hydroxynorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (R)-dehydronorketamine or (S)-dehydronorketamine;iii. Psilocybin or psilocin;iv. LSD;v. DMT;vi. 5-MeO-DMT;vii. DOI;viii. ibogaine or noribogaine;ix. tabernanthalog;x. lithium;xi. tricyclic antidepressant agents;xii. naltrexone;xiii. naloxone;xiv. memantine;xv. riluzole;xvi. lanicemine;xvii. rislenemdaz;xviii. esmethadone;xix. minocycline;xx. melatonin;xxi. butyrate;xxii. anti-inflammatory agents;xxiii. COX-2 inhibitors; and xxiv. galantamine.

11. The compound for use as claimed in any one of claims 1 to 8, or the pharmaceutical composition as claimed in claim 9 or claim 10, formulated in a single dosage form containing a microdose of at least one of the compounds having neurotrophic activity.

12. The compound for use, or the composition, as claimed in claim 11, wherein the microdose comprises a dose in a range from about 1 % to 10% of a pharmacologically active dose of the at least one compound having neurotrophic activity.

13. A substance for use in modifying the course and severity of a long-term neurocognitive disorder caused by activation of the kynurenine pathway in a human or animal subject, the disorder having persisted in the subject for longer than 28 days, wherein the substance comprises a compound selected from the group consisting of ketamine, (R)-ketamine, (S)-ketamine, (R)-norketamine, (2R,6R)-hydroxynorketamine, (S)-norketamine, (2S,6S)-hydroxynorketamine, (R)-dehydronorketamine, (S)-dehydronorketamine and pharmaceutically acceptable salts thereof.

14. The substance for use as claimed in claim 13, wherein the neurocognitive disorder is associated with long COVID.

15. The substance for use as claimed in claim 13 or claim 14, wherein the step of modifying the course and severity of the neurocognitive disorder is performed under conditions effective for an action to cause increased levels of BDNF or GDNF or an action at an ionotropic glutamate receptor.

16. The substance for use as claimed in any one of claims 13 to 15, wherein the substance is administered to the subject via a route selected from the group consisting of oral, transdermal, and any combination thereof.

17. The substance for use as claimed in any one of claims 13 to 16, wherein administration of the substance to the subject is prolonged.

18. The substance for use as claimed in any one of claims 13 to 17, wherein the substance includes at least one further compound or element having neurotrophic activity.

19. The substance for use as claimed in claim 18, wherein the further compound which has neurotrophic activity is psilocybin or psilocin.

20. The substance for use as claimed in any one of claims 13 to 19, wherein the neurocognitive disorder is associated with excess quinolinic acid concentration levels in the subject, and the substance counters, inhibits or suppresses the effects of excess quinolinic acid (QUIN) concentration levels in the subject.