Conjugates and uses thereof

Abstract

The present disclosure provides conjugates comprising at least one psychedelic compound or a precursor thereof and at least one N-methyl D-aspartate (NMD A) receptor (NMD AR) modulator or a precursor thereof, compositions comprising the same and uses thereof.

Description

CONJUGATES AND USES THEREOFTECHNOLOGICAL FIELDThe present disclosure describes conjugates and uses thereof.GENERAL DESCRIPTIONThis invention relates, inter alia, to novel conjugates for use in treating neuropsychiatric and neurologic disorders in patients, including, in particular schizophrenia. In some aspects, this invention relates, inter alia, to novel treatment approaches for chronic schizophrenia patients with negative symptoms.In some aspects of the invention, this invention provides conjugates comprising an agent modulating 5-HT2A receptor function, which can induce psychological effects in the short term with neuroplastic changes in key brain areas in the longer term, specifically and exceptionally through the combinations described herein.According to this aspect, and in some embodiments the conjugate specifically will comprise a psychedelic drug, which can, inter alia, induce characteristic changes in mood, perception and cognition. Classical tryptaminergic psychedelics bind with high affinity to 5- HT2A receptors. Still further according to this aspect, the conjugates of this invention comprise psychedelic drugs that contribute to neuroplasticity, where enhanced synaptic plasticity has been demonstrated in the form of increases in dendritic spines and enhanced neurogenesis.In some aspects of the invention, conjugates comprising a psychedelic, such as psilocybin / psilocin (PSIL) are envisioned for prevention / attenuation of the induction of positive symptoms of schizophrenia.Furthermore, D-serine acts as a co-agonist at the glycine modulatory site of N-methyl- D-aspartate type (NMD A) glutamate receptors (NMD AR), which plays a key role in synaptic adaptation processes and same are hypofunctional in schizophrenia. D-serine may elicit clinical improvements in negative symptoms and overall symptomatology in patients with chronic schizophrenia. D -cycloserine acts as a partial agonist at the glycine modulatory site and has antidepressant and pro-cognitive effects. However so far it has not been envisioned that whenused in combination with a psychedelic, D-serine and D-cycloserine induced improvements, which can be further enhanced.According to this aspect, and in some embodiments, the conjugates of this invention specifically conjugate a psychedelic or any precursor thereof, such as psilocybin / psilocin (PSIL) and a modulator of the of N-methyl-D-aspartate type (NMD A) glutamate receptors (NMD AR) or any precursor thereof, to positively impact neuropsychiatric and neurologic disorders, including schizophrenia, among others. According to some aspects, it is provided a conjugate comprising a first moiety and a second moiety, wherein the first moiety is or comprises a psychedelic drug or any precursor thereof and the second moiety is or comprises an NMDA receptor modulator or a precursor thereof.In some embodied aspects of this invention, the conjugates are specifically cleaved in situ, following administration, and in some embodiments, the conjugates specifically cross the blood-brain barrier, after which, the conjugate undergoes specific cleavage by an appropriate enzyme in nervous tissue, releasing both active components or precursors thereof, namely the psychedelic, such as psilocybin / psilocin (PSIL) or a precursor thereof and a modulator of the of N-methyl-D-aspartate type (NMDA) glutamate receptors (NMD AR) or a precursor thereof, each of which locally and more effectively exerts its therapeutic effect and contributory overall therapeutic combination. It should be noted that in cases where the conjugate comprises a precursor of the NMDA receptor modulator and / or a precursor of the psychedelic drug, after the conjugate is cleaved by an appropriate enzyme, the NMDA receptor modulator precursor and / or the precursor of the psychedelic drug is released and subsequently converted into the active NMDA receptor modulator an / or the active psychedelic drug.Without being bound by theory, and representing certain aspects of the invention, the local delivery of the components of the conjugates promotes the ability of the combination to facilitate the neuroplastic effect of the psychedelic that would improve negative symptoms of schizophrenia and still further enhance neuroplasticity in the brain. For example, and representing certain embodiments, NMDA receptor agonists in the combinations of this invention, may promote neuroplasticity, which may be further promoted in their combination with a psychedelic agent as herein described.In some embodiments, the conjugates of this invention may comprise a psychedelic drug and precursor of the NMDA receptor modulator. In some other embodiments, the conjugates ofthis invention may comprise a precursor of the psychedelic drug and a NMDA receptor modulator.In some aspects, the invention specifically contemplates the local delivery of the components of the conjugates to modulate the function of NMDA receptors in the cortex and other brain areas in combination with psychedelics and, optionally further including agents modulating 5-HT2A receptor function. Concurrent delivery of the two agents (the agents that modulate the function of NMDA receptors in combination with psychedelics) by enzymatic release of the components of the conjugates is specifically envisioned.In one embodiment, this invention provides a conjugate, which in some embodiments, is specifically cleaved once across the blood brain barrier to release the conjugated components of the psychedelic drug or a precursor thereof and an NMDA receptor modulator or a precursor thereof, which in some aspects is an agonist.As noted above, if the conjugate comprises a precursor of a psychedelic drug and / or a precursor of an NMDA receptor modulator, after cleavage by an appropriate metabolizing enzyme present in the body, the psychedelic drug precursor and / or the NMDA receptor modulator precursor is converted to the active agents, e.g. a psychedelic drug and / or a NMDA receptor modulator.Without being bound by theory, in some aspects, the action of the NMDAR agonists / partial agonist component of the conjugate, such as D-serine, (which either forms part of the conjugate or converted from the precursor upon cleavage) is to enhance NMDA receptor signaling in combination with the activity of the released psychedelic drugs (such as but not limited to psilocybin) from the conjugate, in enhancing neuroplasticity. The combination of these two helpful protective effects provides, in some aspects, an improvement superior than any treatment to date, which is further enhanced by the local release of the conjugated combination, in some embodiments, following import of the conjugate across the blood brain barrier (BBB).In another aspect of this invention, there are provided specific conjugates of a psychedelic drug (such as but not limited to psilocybin) and NMDAR agonists / partial agonists, (such as, but not limited to D-serine) for the treatment of depression, and in some embodiments, particularly in treatment-resistant depression.Without being bound by theory, in some aspects, D-serine and D-cycloserine may be effective in beating depression, specifically treatment-resistant depression, whose action may in fact be synergistic when combined with psychedelics, also in some instances reported to be effective in treating depression, specifically treatment-resistant depression. In some aspects of the invention, the concurrent treatment may result in potentiation of NMDA receptor signaling along with enhanced neuroplasticity that could have significant antidepressant effects.Without being bound by theory, in some aspects, another embodied indication for the conjugates of this invention comprising an NMD AR agonist / partial agonist (such as, D-serine) and a psychedelic agent is use in treatment / management / amelioration of symptomatology of posttraumatic stress disorder (PTSD), and in some embodiments, specifically when same is non- responsive to therapy.It will be understood that any conjugate as herein described may be formulated as part of a composition for administration to a subject via any convenient route, which composition is also to be considered as part of this invention.According to these aspects, and in some embodiments, the conjugates / compositions / methods of this invention are particularly useful in treating symptoms of social withdrawal and amotivation, which in some aspects, is associated with negative symptoms in schizophrenia, as well as in subjects suffering from PTSD, and in some embodiments, both groups of subjects may also have a high level of depression comorbidity, which in other aspects is therefore suitable for use with the conjugates / compositions / methods of this invention.In other embodiments, the conjugates / compositions / methods of this invention contemplated include the NMDAR partial agonist D-cycloserine as part of the conjugated molecule. According to this aspect and in some embodiments, D-cycloserine may be conjugated to a psychedelic drug (such as but not limited to psilocybin), which conjugated product / composition comprising same may be particularly useful in the treatment of chronic schizophrenia with prominent negative symptoms, and in some embodiments, for use in treatment-resistant depression and PTSD.In one embodiment, this invention provides a method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with schizophrenia, the method comprising administering to said subject a conjugate as herein described comprising of apsychedelic drug or a precursor thereof and an NMD AR modulator or a precursor thereof as herein described.According to this aspect, and in some embodiments, treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with schizophrenia comprises reducing or abrogating negative symptoms of schizophrenia.In another embodiment, this invention provides a method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with depression, the method comprising administering to said subject a conjugate as herein described or composition comprising same, wherein the conjugate will comprise a psychedelic drug or a precursor thereof and an NMDA receptor agonist or a precursor thereof.In another embodiment, this invention provides a method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with post-traumatic stress disorder, the method comprising administering to said subject a conjugate as herein described or a composition comprising same.In another embodiment, this invention provides a method of enhancing neuroplasticity in a subject with schizophrenia, depression or post-traumatic stress disorder, the method comprising administering to said subject a conjugate as herein described or a composition comprising same.In some aspects, neuroplastic effects may be verified by any means known in the art, for example, as described in WIPO Patent Application Publication Number W 0 / 2021 / 074448, fully incorporated by reference herein.In some embodiments, the NMDA receptor modulator component of the conjugates or the NMDA receptor modulator formed from the precursor as herein described are partial agonists.In other embodiments, this invention specifically contemplates methods of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder, comprising administering to said subject a conjugate of this invention.In some aspects, this invention specifically contemplates a conjugate as herein described for use in the treating, reducing the incidence of, reducing the severity of or improving apathology of a subject with a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder.In accordance with some aspects, it is provided a conjugate comprising at least one psychedelic compound or a precursor thereof and at least one NMDA receptor modulator or a precursor thereof.In accordance with some aspects, it is provided a pharmaceutical composition comprising the conjugate as described herein.In accordance with some aspects, it is provided a conjugate or a composition for use in a method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder, the method comprising administering to said subject the conjugate or the composition.In accordance with some aspects, it is provided a method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder, the method comprising administering to the subject the conjugate or the composition.In accordance with some aspects, it is provided a use of the conjugate for the preparation of a pharmaceutical composition.BRIEF DESCRIPTION OF THE DRAWINGSIn order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of nonlimiting example only, with reference to the accompanying drawings, in which:Figure 1 is a graph showing time course of head twitch response (HTR) for varying doses of 4-OH-DiPT.Figure 2 is a bar graph showing total HTR for varying doses of 4-OH-DiPT.Figure 3 is a graph showing time course of HTR for two doses of 4-OH-DiPT and their equimolar equivalents of HBL20018.Figure 4 is a bar graph showing total HTR for two doses of 4-OH-DiPT and their equimolar equivalents of HBL20018.DETAILED DESCRIPTION OF EMBODIMENTSThe present disclosure provides novel conjugates and compositions comprising same, which are useful for the treatment of various disease, such as neuropsychiatric and neurologic diseases, including, inter alia, schizophrenia, chronic schizophrenia with negative symptoms, post-traumatic stress disorder or depression, as well as treatment-resistant conditions.As described herein, the conjugates include two active compounds or precursors thereof. Specifically, the conjugates comprise at least one psychedelic compound or a precursor thereof and at least one N-methyl D-aspartate receptor (NMD AR) modulator or a precursor thereof.It should be noted that the conjugate may include varying ratios of the active compounds, such that one active compound or precursor thereof may be present in greater or lesser amounts relative to the other. In other words, different stoichiometric rations is possible between the active components or precursors thereof. This flexibility allows the optimization of therapeutic effects, where the proportion of each compound can be tailored to achieve the desired efficacy.Hence, it was suggested that the conjugate is cleaved in situ (in the body), releasing its constituent active compounds to engage their target receptors or pathways. As appreciated, the conjugate described herein can offer several advantages, including, inter alia, enhanced therapeutic efficacy by providing a dual effect, targeting different pathways or mechanisms within the body.In cases where the conjugate includes one or more precursor of the active compounds, these may be further metabolized following cleavage, undergoing enzymatic or chemical transformations to yield their active forms.Interestingly and as shown in Example 2 below, the conjugate exhibits a unique delayed and reduced head twitch response (HTR) compared to each individual compound, resembling a slow-release mechanism. This delayed response likely results from the conjugate's gradual breakdown or dissociation and optionally transformation to an active compound, leading to a controlled, sustained release of the active compounds over time, thereby extending their pharmacological activity.This conjugates’ sequential process of cleavage and possibly transformation may ensure a controlled release and activation of the compounds, potentially reducing required dosage and systemic side effects.Hence, in accordance with some aspects, the present disclosure provides a conjugatecomprising at least one psychedelic compound or a precursor thereof and at least one N-methyl D-aspartate (NMD A) receptor modulator or a precursor thereof.The term conjugate as used herein refers to a to a compound formed by association (linkage) of two or more distinct molecules, such as small molecules, biologies, or drugs. The association in some examples is a covalent association. In some examples, this conjugation may alter the properties of the individual components, potentially enhancing stability, solubility, or therapeutic efficacy, and may result in modified pharmacokinetics, such as delayed release or targeted delivery.In some examples, in the conjugate, the at least one psychedelic compound or a precursor thereof is covalently associated with the at least one NMDA modulator against or a precursor thereof.It should be noted that as also described below, covalently associated may encompasses a direct association as well as an indirect association.As used herein, "direct association" refers to a covalent association between two entities, where they are directly bonded without any intervening molecules or structures, whereas "indirect association" refers to a covalent association wherein the entities are connected through one or more intermediary molecules, structures, or linking groups.In some examples, the at least one psychedelic compound or a precursor thereof is covalently associated with the at least one NMD AR modulator or a precursor thereof.The present disclosure is not limited to a psychedelic compound and is applicable for various psychedelic compounds.The term psychedelic compound, as used herein, refers to a substance that primarily affects perception, cognition, and mood by interacting with neurotransmitter systems in the brain. These compounds typically induce altered states of consciousness, sensory distortions, and changes in thought patterns or mood.In some examples, the psychedelic compound or a precursor thereof is a serotonergic psychedelic compound or a precursor thereof.A serotonergic psychedelic compound, as used herein, refers to a type of psychedelic substance that exerts its effects primarily by interacting with the serotonin (5-HT) system, particularly the 5-HT2A receptor in the brain.In some aspects of the invention, the conjugates comprises an agent modulating 5-HT2A receptor function, which can induce psychological effects in the short term with neuroplastic changes in key brain areas in the longer term, specifically and exceptionally through the conjugates described herein.In some examples, the psychedelic compound or a precursor thereof is a 5-HT2A receptor modulator.Hence, in accordance with some aspects, the present disclosure provides a conjugate comprising at least one 5-HT2A receptor modulator or a precursor thereof and at least one NMD AR modulator or a precursor thereof.In some examples, the at least one 5-HT2A receptor modulator or a precursor thereof is associated with said at least one NMD AR modulator or a precursor thereof.5-HT2A receptor as used herein refers to a subtype of the serotonin receptor family (5- HT receptors) that is classified as a G protein-coupled receptor (GPCR) that binds serotonin (5- hydroxytryptamine, or 5-HT), a key neurotransmitter involved in various physiological, psychological and behavioral processes.The term modulating 5-HT2A receptor or 5-HT2A receptor modulator as used herein, refers to the ability of a compound disclosed herein to alter the function of 5-HT2A receptor, for example, by increasing or decreasing the direct or indirect interaction between a 5-HT2A receptor and a ligand, such as a natural or synthetic binding ligand.A 5-HT2A receptor modulator may increase the activity or inhibit the activity of a 5- HT2A receptor by acting as an agonist or antagonist of the 5-HT2A receptor.In some examples, the psychedelic compound or a precursor thereof is a 5-HT2A receptor agonist.The 5-HT2A receptor agonist in accordance with the present disclosure encompasses full agonist, partial agonist, and allosteric agonist.The term full agonist and specifically in connection with the 5-HT2A receptor refers to a compound that binds to the receptor and activates it fully, resulting in a maximum biological response.The term partial agonist and specifically in connection with the 5-HT2A receptor refers to a compound that binds to the receptor and induces a weaker response than a full agonist, evenif all receptors are occupied. It should be noted that at times partial agonists are used to allow activation of the receptor without overstimulation, potentially reducing side effects.The term allosteric agonist and specifically in connection with the 5-HT2A receptor refers a compound that binds to a different site on the 5-HT2A receptor (not the primary serotonin-binding site) and modulates its activity.In some embodiments, the psychedelic drug is one such that is described in US- 2009203750-A1, AU-2005300045- Al, AU-2009214724-Al, US-2019201402-A1, WO- 2022067165-A1, US-11254640-B2, EP-3519816-Al, WO-2021076572-A1 or WO- 2020176599-A1, which are hereby incorporated by reference in their entirety, may be included, as well.According to this aspect and in some embodiments, the serotonergic psychedelic (serotonin 5-HT2A receptor agonists) may comprise: Tryptamines (such as, in some embodiments, alkylated tryptamines]) such as Psilocin, also known as '4-HO-DMT'; Psilocybin, also known as '4-PO-DMT'; the primary active constituent of the Psilocybe genus of mushrooms; its effects are mostly attributed to psilocin, to which it is a prodrug via dephosphorylation; Bufotenin, also known as '5-HO-DMT' and dimethylserotonin; another constituent of the skin and venom of psychoactive toads, also a metabolite of 5-MeO-DMT; Baeocystin, also known as '4-PO-NMT'; another active constituent of the Psilocybe genus of mushrooms; Aeruginascin, also known as '4-PO-N-TMT, an active constituent of the mushroom Inocybe aeruginascens; 5-MeO-DMT, the primary active constituent of the skin and venom of psychoactive toads, a prodrug to bufotenin via demethylation; N,N-Dimethyltryptamine, also known as 'DMT'; the primary active constituent of the Amerindian brew ayahuasca; endogenously present in various plants and animals, including humans; 5-Bromo-DMT, found in the marine invertebrates Smenospongia aurea and Smenospongia echina, as well as in Verongula rigida; N-Methyl-N-ethyltryptamine, also known as 'MET'; N-Methyl-N- isopropyltryptamine, also known as 'MiPT'; N-Methyl-N-propyltryptamine, also known as 'MPT'; N,N-Diethyltryptamine, also known as 'DET'; N-Ethyl-N-isopropyltryptamine, also known as 'EiPT'; N-Methyl-N-butyltryptamine, also known as 'MBT'; N-Propyl-N- isopropyltryptamine, also known as 'PiPT'; N,N-Dipropyltryptamine, also known as 'DPT',N,N-Diisopropyltryptamine, also known as 'DiPT'; N,N-Diallyltryptamine, also known as 'DALT'; N,N-Dibutyltryptamine, also known as 'DBT'; N-Ethyltryptamine, also known as 'NET'; N-Methyltryptamine, also known as 'NMT'; Trimethyltryptamine, also known as 'TMT'(2,N,N-TMT, 5,N,N-TMT, and 7,N,N-TMT); a-Methyltryptamine, also known as 'YMT and 'AMT'; also has entactogenic properties; a-Ethyltryptamine, also known as 'aET' and 'AET'; also has entactogenic properties; a,N-DMT; a,N,N-Trimethyltryptamine, also known as 'a- TMT; Ethocybin, also known as '4-PO-DET', 'CEY-19', and 'CEY-39'; 4-HO-MET, also known as 'Metocin', 'Methylcybin', and 'Colour'; 4-HO-DET, also known as 'Ethocin' and 'CZ-74'; 4- HO-MPT, also known as 'Meprocin'; 4-HO-MiPT, also known as 'Miprocin'; 4-HO-MALT; 4- HO-DPT, also known as 'Deprocin'; 4-HO-DiPT, also known as 'Iprocin'; 4-HO-DALT, also known as ‘Daltocin’; 4-HO-DBT; 4-HO-DSBT; 4-HO-aMT; 4-HO-MPMI, also known as 'Lucigenol'; 4-HO-TMT; 4-H0-l,N,N-TMT, also known as T-Me-4-HO-DMT' and T- methylpsilocin'; 4-HO-5-MeO-DMT, also known as 'Psilomethoxin'; 4-AcO-DMT, also known as 'psiloacetin'; its effects are partially attributed to psilocin, to which it is a prodrug via deacetylation; 4-AcO-MET, also known as 'Metacetin'; 4-AcO-MiPT; 4-AcO-MALT; 4-AcO- DET, also known as 'Ethacetin'; 4-AcO-EiPT, also known as 'Ethipracetin'; 4-AcO-DPT, also known as 'Depracetin'; 4-AcO-DiPT, also known as 'Ipracetin'; 4-AcO-DALT, also known as 'Daltacetin'; 4-MeO-DMT; 4-MeO-MiPT; 5-MeO-NMT; 5-MeO-MET; 5-MeO-MPT; 5-MeO- MiPT, also known as 'Moxy'; also has entactogenic properties; 5-MeO-MALT; 5-MeO-DET; 5- MeO-EiPT; 5-MeO-EPT; 5-MeO-PiPT; 5-MeO-DPT; 5-MeO-DiPT, also known as 'Foxy Methoxy'; 5-MeO-DALT; 5-MeO-aMT, also has entactogenic properties; 5-MeO-aET, also has entactogenic properties; 5-MeO-MPMI; 5-MeO-2,N,N-TMT , also known as 'Indomethacin' and 'Indapex'; 5-MeO-7,N,N-TMT; 5-MeO-a,N-DMT, also known as 'a,N,O-TMS'; 4-F-5-MeO- DMT; 5-MeS-DMT; 5-Me-MiPT; 5-HO-DiPT; 2-a-DMT; 2-Me-DET; 4-Me-aMT; 4-Me-aET, also has entactogenic properties; 7-Me-aET, also has entactogenic properties; 4,5-DHP-AMT, also known as 'AL-37350A'; 4,5-DHP-DMT; 4,5-MDO-DMT; 4,5-MDO-DiPT; 5,6-MDO- DiPT; 5,6-MDO-MiPT; 5-Fluoro-aMT, also has entactogenic properties; 6-Fluoro-aMT; 6- Fluoro-DMT; N,N-Tetramethylenetryptamine, also known as 'Pyr-T'; 4-HO-pyr-T; 5-MeO-pyr- T; RU-28306, also known as '4,a-Methylene-N,N-DMT'; 0-4310, also known as '6-Fluoro-l- Isopropyl-4-HO-DMT'; CP-132,484, also known as '4,5-DHP-l-Methyltryptamine', or combinations thereof.In some embodiments, the serotonergic psychedelics (serotonin 5-HT2A receptor agonists) contemplated for the combinations, compositions, of this invention, or for use in the methods or therapeutic uses as herein described, may include: Benzofuran derivatives; Dimemebfe, also known as '5-MeO-BFE'; 5-MeO-DiBF; Ibogoids; Ibogaine, the primary activeconstituent of iboga rootbark; also has dissociative properties; Voacangine, another active constituent of iboga rootbark; Ergolines; Lysergic acid diethylamide, also known as 'LSD' and 'acid'; Lysergic acid amide, also known as 'LSA' and 'ergine'; the primary active constituent of morning glory and Hawaiian baby woodrose seeds; N1 -Methyl-lysergic acid diethylamide, also known as 'MLD-41'; N- Acetyl-lysergic acid diethylamide, also known as 'ALD-52'; 1- Propionyl-lysergic acid diethylamide, also known as '1P-LSD'; its effects are partially attributed to LSD, to which it is a prodrug via hydrolyzation; 1 Dcyclopropanoyl-d-lysergic acid diethylamide, also known as '1 cP- LSD'; 1-valeryl-D-lysergic acid diethylamide, also known as '1V-LSD'; 6-Allyl-6-nor-lysergic acid diethylamide, also known as 'AL-LAD'; 6-Butyl-6-nor- lysergic acid diethylamide, also known as 'BU-LAD'; 6-Ethyl-6-nor-lysergic acid diethylamide, also known as 'ETH-LAD'; l-Propionyl-6-Ethyl-6-nor-lysergic acid diethylamide, also known as '1P-ETH-LAD'; 6-Propyl-6-nor-lysergic acid diethylamide, also known as 'PRO-LAD'; 6- Cyclopropyl-6-nor-lysergic acid diethylamide, also known as 'CYP-LAD'; 6-nor-Lysergic acid diethylamide, also known as 'PARGY-LAD'; Lysergic acid ethylamide, also known as 'LAE- 32'; Lysergic acid ?-hydroxyethylamide, also known as 'LSH' and 'LAH'; another active constituent of morning glory seeds; an active constituent of some species of fungi; Lysergic acid 2-butyl amide, also known as 'LSB'; Lysergic acid 3-pentyl amide, also known as 'LSP'; Lysergic acid methyl ester, also known as 'LSME'; Lysergic acid 2,4-dimethylazetidide, also known as 'LSZ' and 'LA-SS-Az'; Lysergic acid piperidine, also known as 'LSD-Pip'; N,N-Dimethyl- lysergamide, also known as 'DAM-57'; Methylisopropyllysergamide, also known as 'MIPLA'; N,N-Diallyllysergamide, also known as 'DAL'; N-Pyrrolidyllysergamide, also known as 'LPD- 824'; N-Morpholinyllysergamide, also known as 'LSM-775'; 1 -methyl-lysergic acid butanolamide, also known as 'Methysergide'; the active constituent of Sansert and Deseril; a prodrug which has to be metabolized to methylergometrine to become psychoactive; Lysergic acid ?-propanolamide, also known as 'Ergonovine' and 'Ergometrine'; another active constituent of morning glory seeds, and an active constituent of ergot fungi’ Lysergic acid 1 -butanolamide, also known as 'Methylergonovine', 'Methergine', and 'Methylergometrine'; another active constituent of morning glory seeds and of ergot fungi; Phenethylamines (more specifically alkoxylated phenethylamines); or combinations thereof.In some embodiments, the serotonergic psychedelics (serotonin 5-HT2A receptor agonists) contemplated for t this invention, or for use in the methods or therapeutic uses as herein described, may include: Substituted phenethylamines; Mescaline, the primary active constituent of certain cacti, such as peyote and San Pedro; Lophophine, also known as 'MMDPEA'; anotheractive constituent of certain cacti, such as peyote and San Pedro; also has entactogenic properties; Isomescaline; Cyclopropylmescaline; Thioisomescaline (2-TIM, 3-TIM, and 4- TIM); 4-Desoxymescaline; Jimscaline; Escaline; Metaescaline; Thiometaescaline (3-TME, 4- TME, and 5-TME); Trisescaline; Thiotrisescaline (3-T-TRIS and 4-T-TRIS); Symbescaline; Asymbescaline; Thiosymbescaline (3-TSB and 4-TSB); Phenescaline; Allylescaline, also known as 'AL'; Methallylescaline; Proscaline; Isoproscaline; Metaproscaline; Thioproscaline; Buscaline; Thiobuscaline; a-ethylmescaline, also known as 'AEM'; Ariadne, also known as ' a - Et-DOM', '4C-D', and 'Dimoxamine'; Macromerine; MEPEA; TOM (2-TOM and 5-TOM); Bis- TOM; TOMSO, also known as '2-methoxy-4-methyl-5-methylsulfinylamphetamine'; TOET (2- TOET and 5-TOET); BOH; BOM, also known as ' p -Methoxy-mescaline'; -D; 4-D; DME; F- 2; F-22; FLEA, also known as 'MDHMA'; MDPH; MDMP; Propynyl; 2C family (2,5- dimethoxy, 4-substituted phenethylamines); Dk-2C-B; 2C-B; 2CB-2EtO; 2CB-5EtO; 2CB- diEtO; 2C-B-FLY; 2C-B -BUTTERFLY; 2C-C; 2C-D; 2CD-2EtO; 2CD-diEtO; 2CD-5EtO; 2C- E; 2C-EF; 2C-F; 2C-G (2C-G-1, 2C-G-2, 2C-G-3, 2C-G-4, 2C-G-5, 2C-G-6, and 2C-G-N); 20- H; 2C-I; 2CL2EtO; 2C-iP; 2C-N; 2C-O; 2C-O-4; 2C-P; 2C-SE; 2C-T; 2CT-5EtO; 2C-T-2; 2CT- 2-2EtO; 2CT-2-5EtO; 2CT-2-diEtO; 2C-T-4 (2C-T-4 and 7-2C-T-4); 2CT-4-2EtO; 2C-T-7; 2CT-7-2EtO; 2C-T-8; 2C-T-9; 2C-T-13; 2C-T-15; 2C-T-16; 2C-T-17; 2C-T-19; 2C-T-21; 2C- TFM; 2C-YN; BOB, also known as 'P -Methoxy-2C-B'; BOD, also known as ' p -Methoxy-2C- D'; BOHD, also known as 'P -Hydroxy-2C-D'; HOT-2; HOT-7; HOT- 17; Indane derivatives; 2CB-Ind; Benzocyclobutene derivatives; 2C-BCB, also known as 'TCB-2'; NBOMe derivatives; NBOMe-mescaline; 2C-H-NB0Me, also known as '25H-NBOMe'; 2C-C-NB0Me, also known as '25C-NBOMe'; 2CBCB-NB0Me, also known as 'NBOMe-TCB-2'; 2CBFly-NB0Me, also known as 'Cimbi-3T; 2C-B-NB0Me, also known as '25B-NBOMe', 'M25B-NBOMe', 'BOM 2- CB', 'Cimbi-36', 'Nova', or 'New Nexus'; 2C-I-NB0Me, also known as '251-NBOMe', 'Cimbi-5', "Solaris", or "N-Bomb"; 2C-TFM-NB0Me, also known as '25TFM-NBOMe'; 2C-D-NB0Me, also known as '25D-NBOMe'; 2C-G-NB0Me, also known as '25G-NBOMe'; 2C-E-NB0Me, also known as '25E-NBOMe'; 2C-P-NB0Me, also known as '25P-NBOMe'; 2C-iP-NB0Me, also known as '25iP-NBOMe'; 2C-CN-NB0Me, also known as '25CN-NBOMe'; 2C-N- NBOMe, also known as '25N-NBOMe'; 2C-T-NB0Me, also known as '25T2-NBOMe'; 2C-T- 4-NB0Me, also known as '25T4-NBOMe'; 2C-T-7-NBOMe, also known as '25T7-NBOMe'; DMBMPP, 2-Benzylpiperidine analogue of 25B-NBOMe; NBOH derivatives; 2C-C-NB0H, also known as '25C-NBOH' and 'NB0H-2CC; 2C-B-NB0H, also known as '25B-NBOH'; 2C- I-NBOH, also known as '25I-NBOH'; 2C-CN-NB0H, also known as '25CN-NBOH' and'NB0H-2C-CN'; NBMD derivatives; 2C-I-NBMD, also known as '25I-NBMD'; NBF derivatives; 2C-C-NBF, also known as '25C-NBF'; 2C-B-NBF, also known as '25B-NBF'; 2C- I-NBF, also known as '25I-NBF'; Substituted amphetamines (alpha-methyl-phenethylamines); 3C family (3,5-dimethoxy, 4-substituted amphetamines); 3C-E; 3C-P; 3C-DFE; 3C-BZ; DOx family (2,5-dimethoxy, 4-substituted amphetamines); DOAM; DOB; Meta-DOB; Methyl-DOB; DOBU; DOC; DOEF; DOET, also known as 'DOE'; DOI’ DOM, also known as 'STP'; -DOM; DON; DOPR; DOiPR; DOT, also known as 'Aleph' (Aleph-2, Aleph-4, Aleph-6, and Aleph-7); Meta-DOT; Ortho-DOT; DOTFM; Phenylcyclopropylamine derivatives; DMCPA; DMMDA; DMMDA-2; 2,5-dimethoxy-3,4-dimethylamphetamine, also known as 'Ganesha'; (G-3, G-4, G- 5, and G-N); 4-methyl-2,5-dimethoxymethamphetamine, also known as 'Beatrice', 'MDO-D', and 'MDOM'; 2,N-dimethyl-4,5-methylenedioxyamphetamine, also known as 'Madam-6'; Dimethoxyamphetamine (2,4-DMA, 2,5-DMA, and 3,4-DMA); Trimethoxyamphetamine (TMA-2, TMA-6); Tetramethoxy amphetamine; Br-DragonFLY; TFMFly; 2-Bromo-4,5- methylenedioxy amphetamine; 4-Bromo-3,5-dimethoxyamphetamine; EEE; EEM; EME; EMM; EDMA; EIDA; Ethyl-J, also known as 'EBDB'; Methyl-J, also known as 'MDMB'; Ethyl-K, also known as 'EBDP'; Methyl-K, also known as 'MBDP' and 'UWA-9T; IDNNA; Iris; MDAI; MDMAI; MDAT; MDMAT; MDAL; MDBU; MDBZ; MDDM; MDIP; MDMEOET; MDMEO; MDOH, also known as 'MDH'; MDHOET; MDPL; MDCPM; MDPR; MEDA; MEM; Methyl-DMA; MDA, also known as '3-methoxy-MDA' (2T-MMDA-3a and 4T-MMDA- 2); MMDA-2; 5-Methyl-MDA; MEE; MME; MPM; DiFMDA; 5-APB; 6-APB, also known as ’Benzofury’; 5-APDB; 6-APDB; 5-MAPB; 5-MAPDB; 6-MAPDB; 6-MAPB; 6-EAPB; 5- EAPB; Para-Methoxy amphetamine, also known as 'PMA' and '4-MA'; Paramethoxymethamphetamine, also known as 'PMMA', 'Methyl-MA', and '4-MMA'; 4- Ethylamphetamine, also known as '4-EA'; 3-Methoxy-4-methylamphetamine, also known as 'MMA'; 4-Methylmethamphetamine, also known as '4-MMA'; 4-Methylthioamphetamine, also known as '4-MTA'; 4-Fluoroamphetamine, also known as '4-FA', 'PAL-303', 'Flux', 'Flits', 'R2D2', and 'Miley'; Norfenfluramine, also known as '3-TFMA'; Para-Iodoamphetamine, also known as 'PIA', '4-iodoamphetamine', and '4-IA'; Para-Chloroamphetamine, also known as 'PCA', '4-chloroamphetamine', and '4-CA'; Benzoxazines (for example, cyclopropylethynylated benzoxazines); Substituted benzoxazines; Efavirenz, the active constituent of Sustiva, Stocrin, and Efavir; or any combinations thereof.In some embodiments, the conjugate comprises a psychedelic drug, which can, inter alia, induce characteristic changes in mood, perception and cognition.In some examples, the psychedelic compound or a precursor thereof is one or more of a tryptamine compound or precursor thereof, a phenethylamine compound or precursor thereof, a lysergamide compound or precursor thereof, an ergoline compound or precursor thereof, or any combination thereof.A tryptamine compound as used herein refers to a class of molecules derived from tryptamine, a naturally occurring monoamine alkaloid.In some examples, the psychedelic compound or a precursor thereof is a tryptamine compound or precursor thereof. In some examples the psychedelic compound or a precursor thereof is selected from the group consisting of psilocybin (4-phosphoryloxy- / V, / V- dimethyltryptamine), Dimethyltryptamine (DMT), 5-Methoxy-N,N-dimethyltryptamine (5- MeO-DMT), 5-MeO-DiPT (5-Methoxy-Diisopropyltryptamine), 4-AcO-DMT (4-Acetoxy- Dimethyltryptamine), DiPT (N,N-Diisopropyltryptamine), DET (Diethyl tryptamine), 4-HO- MiPT (4-Hydroxy-N-Methyl-N-Isopropyltryptamine), 4-AcO-MiPT (4-Acetoxy-N-Methyl-N- Isopropyltryptamine), 5-MeO-MiPT (5-Methoxy-N-Methyl-N-Isopropyltryptamine), Bufotenin (5-hydroxy-N, N-dimethyl tryptamine), 4-HO-MET (4-Hydroxy-N-Methyl-N-Ethyltryptamine), AMT (Alpha-Methyltryptamine), 4-HO-DiPT (4-Hydroxy-N,N-Diisopropyltryptamine) or any combination thereof.In some examples, the tryptamine compound or precursor thereof is psilocybin (psilocin or PSIL) or a precursor thereof.In some examples, the tryptamine compound or precursor thereof is 4-HO-DiPT or a precursor thereof.4-HO-DiPT also known by a chemical name 4-Hydroxy-N,N-Diisopropyltryptamine, has the following structure:In some examples, the psychedelic compound or a precursor thereof is a phenethylamine compound or precursor thereof selected from the group consisting of Mescaline, 2C-B, DOx series, 3,4-methylenedioxymethamphetamine (MDMA) or a combination thereof.In some examples, the psychedelic compound or a precursor thereof is a phenethylamine compound or precursor thereof. In In some examples, the psychedelic compound or a precursor thereof is selected from the group consisting of AL-LAD, LSA, Lysergic acid diethylamide (LSD) or any combination thereof.In accordance with some aspects, the present disclosure provides a conjugate comprising at least one tryptamine compound or precursor thereof and at least one NMD AR modulator or a precursor thereof.In accordance with some aspects, the present disclosure provides a conjugate comprising at least 4-HO-DiPT or precursor thereof and at least one NMD AR modulator or a precursor thereof.As described herein, the present disclosure encompasses a precursor thereof of a psychedelic drug.The term “precursor thereof of a psychedelic drug” as used herein refers to a precursor of a psychedelic drug, which upon cleavage (breakdown) of the conjugate by metabolizing enzyme, is transformed into the psychedelic drug. As described herein, metabolic scission of the conjugate may occur in site, releasing the psychedelic drug precursor that may be aromatized by an enzyme (such as cytochrome P450) to produce the psychedelic drug, for example, through a dehydrogenation pathway.The term precursor thereof in accordance with some examples may be considered as a moiety thereof as well as prodrugs thereof.In some examples, in which the psychedelic drug comprises a tryptamine core (i.e. having an indole core), the precursor thereof comprises an indoline core.In some examples, the precursor of a psychedelic drug has an indoline core.In some examples, in which the psychedelic drug has an indole core, the precursor thereof of a psychedelic drug has an indoline core.It should be noted that any precursor thereof of a psychedelic drug may undergo transformation (be transformed) in situ to produce the psychedelic drug.Example structures of precursor thereof of a psychedelic drug are shown herein below.As described herein, the conjugates of this invention comprise one or more NMD AR modulators. The one or more NMDAR modulators may be similar NMDAR modulators ordifferent NMD AR modulators.NMD AR as used herein refers to a subtype of glutamate receptor in the brain that have a crucial role in regulating synaptic plasticity, learning, and memory by controlling the flow of ions through the cell membrane and may be activated by the neurotransmitter glutamate and a co-agonist (such as glycine or D-serine).The term modulator as used herein refers to a compound or drug that binds to a receptor and alters its activity by either enhancing or inhibiting the receptor’s function. The modulator may induce an increase in activity or a decrease in activity. In the context of the present disclosure, the NMDAR modulator refers to a substance that influences the activity of NMDARs. The modulator encompasses direct modulation as well as indirect modulation, namely by fine-tune the receptor's response to its natural ligand.In some examples, the conjugate comprising a psychedelic drug and an NMD A receptor modulator.In some examples, the conjugate comprising a psychedelic drug and a precursor of an NMDA receptor modulator.In some examples, the conjugate comprising a precursor of a psychedelic drug and an NMDA receptor modulator.In some examples, the conjugate comprising a psychedelic drug and a precursor of an NMDA receptor modulator.In some examples, the conjugate comprising a precursor of a psychedelic drug and a precursor of an NMDA receptor modulator.In some examples, the NMDAR modulator is a positive modulator, a negative modulator or an allosteric modulator.In some examples, the NMDAR modulator is an agonist or an antagonist.The present disclosure is not limited to a specific NMDA receptor modulator and is applicable to various NMDA receptor modulators that as described herein in accordance with some examples, may be one or more NMDA receptor agonist or partial agonist.In some examples, the NMDAR modulator is a full agonist or a partial agonist.In some examples, the NMDAR modulator or a precursor thereof is a NMDAR full agonist or a NMDA receptor partial agonist.It should be noted that when referring to a NMDA receptor agonist it refers to a full agonist as well as partial agonist.In accordance with some aspects, the present disclosure invention provides a conjugate comprising a psychedelic drug or a precursor thereof and an NMDA receptor modulator or a precursor thereof, which in some embodiments, the NMDA receptor modulator is a full agonist or a partial agonist.In accordance with some aspects, the present disclosure provides a conjugate comprising at least one tryptamine compound or precursor thereof and at least one NMD AR agonist or a precursor thereof.In accordance with some aspects, the present disclosure provides a conjugate comprising at least 4-HO-DiPT or precursor thereof and at least one NMD AR agonist or a precursor thereof.The term full agonist and specifically in connection with the NMD AR refers to a compound that binds to the receptor and activates it fully, resulting in a maximum biological response.The term partial agonist and specifically in connection with the NMD AR refers to a compound that binds to the receptor and induces a weaker response than a full agonist, even if all receptors are occupied. It should be noted that at times partial agonists are used to allow activation of the receptor without overstimulation, potentially reducing side effects.In some embodiments, the NMD AR agonist is glycine or in some embodiments, the NMDA receptor agonist is Alanine (D-alanine, L-alanine), or in some embodiments, the NMDA receptor agonist is Milacemide, or in some embodiments, Sarcosine (monomethylglycine), or in some embodiments, the NMDA receptor agonist is L-Serine.In some embodiments, the NMDA receptor agonist is 3,5-Dibromo-L-phenylalanine, Aminocyclopropanecarboxylic acid (ACC), or rapastinel (GLYX-13) or apimostinel (NRX- 1074), or HA-966, or Homoquinolinic, or Zelquistinel (AGN-241751), or Apimostinel (NRX- 1074) or others known in the art.In some embodiments, deuterated forms of the amino acids described herein are specifically contemplated for use. For example, and in some embodiments, the deuterated form of is deuterated D-serine.In some examples, the NMDA receptor agonist or a precursor thereof is one or more of glutamate, glycine, Alanine (D-alanine, L-alanine), D-Serine, Milacemide, L-Aspartate, D-Cycloserine, 1 -Aminocyclopropane- 1 -carboxylic acid (ACPC), Sarcosine, Rapastinel, a precursor thereof or any combinations thereof.In some embodiments, the NMDA receptor agonist or a precursor thereof is 3,5- Dibromo-L-phenylalanine, Aminocyclopropanecarboxylic acid (ACC), or rapastinel (GLYX- 13) or apimostinel (NRX-1074), or HA-966, or Homoquinolinic, or Zelquistinel (AGN-241751), or Apimostinel (NRX-1074) or others known in the art a precursor thereof or any combinations thereof.In some embodiments, the NMDA receptor agonist or a precursor thereof is glutamate, NMDA, D-serine, glycine, aspartate, quisqualic acid, a precursor thereof or any combinations thereof.In some examples, NMDA receptor agonist or a precursor thereof activates the glycine modulation site (GMS) of the NMD AR.In some examples, the NMDA receptor agonist or a precursor thereof is a GSM agonist.The GMS of the NMD AR (also denoted at times as glycine binding site) is a regulatory site located on the receptor's NR1 subunit.In some examples, NMDA receptor agonist or a precursor thereof is one or more of glycine, D-Serine, L-Aspartate, D-Cycloserine, 1 -Aminocyclopropane- 1 -carboxylic acid (ACPC), Sarcosine, Rapastinel, a precursor thereof or any combinations thereof.In some other examples, the NMDA receptor agonist or a precursor thereof is D-Serine, D -cycloserine, a precursor thereof or any combinations thereof.As known, D-cycloserine (DCS) and D-serine both acts as co-agonists at the NMD AR but have different mechanisms of action and effects.It was suggested that as D-serine acts as a full co-agonist at the glycine-binding site of the NMD AR, upon binding to this site, it allows the receptor to be fully activated by glutamate, whereas D-cycloserine (DCS) acts as a partial agonist at the same glycine-binding site on the NMD AR and enhances receptor activation but to a lesser extent compared to D-serine. It was suggested that this difference have an advantageous in preventing overstimulation of the receptor.In some other examples, the NMD AR agonist or a precursor thereof is D-Serine.D-serine is known to act as a co-agonist at the GSM of the NMDAR. D-serine may elicitclinical improvements in negative symptoms and overall symptomatology in patients with chronic schizophrenia, but so far it has not been envisioned that conjugation of the NMD AR modulator with a psychedelic, will yield still greater improvements than any treatment to date.In some other examples, the NMDA receptor agonist or a precursor thereof is D- cycloserine.In accordance withs some aspect, it is provided a conjugate comprising at least one psychedelic compound or a precursor thereof and at least one NMD AR agonist or a precursor thereof, wherein the NMDAR agonist or a precursor thereof is D-Serine, D-cycloserine, a precursor thereof or any combinations thereof.In accordance withs some aspect, it is provided a conjugate comprising at least one psychedelic compound or a precursor thereof and at least one NMDAR agonist or a precursor thereof, wherein the psychedelic compound or a precursor thereof is 4-HO-DiPT or a precursor thereof and the NMDAR agonist or a precursor thereof is D-Serine, D-cycloserine, a precursor thereof or any combinations thereof.In accordance with examples, the conjugate comprises 4-HO-DiPT or a precursor thereof and D-serine or a precursor thereof. In some examples, 4-HO-DiPT or a precursor thereof is covalently associated with D-serine or a precursor thereof.In accordance with some examples, the conjugate comprises 4-HO-DiPT or a precursor thereof and D-cycloserine or a precursor thereof. In some examples, 4-HO-DiPT or a precursor thereof is covalently associated with D-cycloserine or a precursor thereof.According to this aspect, and in some embodiments, the conjugates of this invention specifically conjugate a psychedelic drug or a precursor thereof, such as psilocybin / psilocin (PSIL) and a modulator of the of N-methyl-D-aspartate type (NMDA) glutamate receptors (NMDAR) or a precursor thereof, to positively impact neuropsychiatric and neurologic disorders, including schizophrenia, among others.In PCT International Application Number PCT / IL2023 / 050919, the combination inter alia, of psilocybin and NMDAR agonists was described as a useful therapy, which disclosure is fully incorporated herein by reference.As described herein, the present disclosure encompasses a precursor thereof of a NMDAR modulator. The term “precursor thereof of a NMDAR modulator” as used herein refers to a precursor of a NMDA receptor modulator (e.g. agonist), which upon cleavage (breakdown)of the conjugate by metabolizing enzyme, is transformed into the NMDA receptor modulator (e.g. agonist).As described herein, metabolic scission of the conjugate may occur in site, releasing the NMDA receptor modulator precursor that further may undergo conversion to thereby from the NMDA receptor modulator, e.g. D-Serine.In some examples, in which the NMDAR agonist is D-serine, the precursor thereof may be an oxazolidin-2-one moiety.In some examples, the D-serine precursor comprises an oxazolidin-2-one moiety.In some examples, the D-serine precursor has the following structure:wherein the curved line represented the connection point.In some examples, the D-serine precursor is converted to D-serine.In some examples, the D- cycloserine precursor is converted to D- cycloserine.The term precursor thereof in accordance with some examples may be considered as a moiety thereof as well as prodrugs thereof.Example structures of precursor thereof of a NMDAR modulator are shown herein below.Without being bound by theory, and representing certain aspects of the invention, it has been found that the conjugates of this invention promote direct blood-brain barrier (BBB) crossing of the conjugates of this invention, whereinafter crossing the BBB, the psychedelic drug or a precursor thereof and NMDAR modulator components or a precursor thereof are released in active form, at the target site, providing local efficient delivery for enhanced efficacy.In some embodied aspects of this invention, the conjugates are specifically cleaved in situ, following administration, and in some embodiments, the conjugates specifically cross the blood-brain barrier, after which, the conjugate undergoes specific cleavage in nervous tissue, releasing both active components, the psychedelic drug or any precursor thereof, such as psilocybin / psilocin (PSIL) and a modulator of the of N-methyl-D-aspartate type (NMDA) glutamate receptors (NMDAR) or any precursor thereof, each of which locally and moreeffectively exerts its therapeutic effect and contributory overall therapeutic combination.Without being bound by theory, and representing certain aspects of the invention, the local delivery of the components of the conjugates promotes the ability of the combination to facilitate the neuroplastic effect of the psychedelic that would improve negative symptoms of schizophrenia and still further enhance neuroplasticity in the brain. For example, and representing certain embodiments, NMDA receptor agonists in the combinations of this invention, may promote neuroplasticity, which may be further promoted in their combination with a psychedelic agent as herein described.According to this aspect, it is now for the first time contemplated making use of conjugates comprising an NMD AR agonist, such as D-serine, or a precursor thereof to elicit clinical improvements in negative symptoms and overall symptomatology in patients with chronic schizophrenia, as part of a conjugate with a psychedelic drug or a precursor thereof, for in situ release, as part of the combination therapies described herein.In some embodiments, the conjugate of this invention prevents the psychedelic effects of the psychedelic drug, while at the same time allowing the neuroplastic effect of the psychedelic drug. In some embodiments, such conjugate, improve outcomes in different neuropsychiatric and neurologic diseases and conditions, including, inter alia, improving negative symptoms of schizophrenia.In accordance with some aspects, the present disclosure provides a conjugate having a structure of Formula la:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K is a point of connectivity to at least one NMDA receptor agonist or a precursor thereof, q is 0, 1, 2, 3, or 4,Li is -(CH2)m-,-C(0)-, -0-, -NH-, -O-CH2-, -N-(CH2)m-, -NH-C(O)-, each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6,Ri and R2 are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, Ci- C12 haloalkyl, R7 if present, is independently hydrogen, deuterium, cyano, amino, amide, nitro, hydroxy, acetoxy, oxo, halo, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 haloalkenyl, C2-Ci2alkynyl, C2-C12 haloalkynyl, C1-C12 alkoxy, C1-C12 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, trifluoromethyl, n is selected from 0, 1, 2, 3, or 4.In accordance with some aspects, the present disclosure provides a conjugate having a structure of Formula lb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K, q, Li, m, Ri, R2, R7 and n are as detailed above for Formula (la).In some examples, in which the conjugate is defined structure by Formula (la) or Formula (lb), R7 if present, is independently hydrogen, deuterium, hydroxy, acetoxy, C1-C12 alkyl, C1-C12 alkoxy. In some examples, in which the conjugate is defined structure by Formula (la) or Formula (lb), n is selected from 0, 1, 2, 3, or 4.In some examples, in conjugates having structure (la) or (lb), q+n=4. In some examples, in conjugates having structure (la) or (lb), q is 0 and n is 4. In some examples, in conjugates having structure (la) or (lb), n is 0 and q is 4.It should be further noted that the substitution represented by R7 if present (namely in case n is not 0) may include one or more of the substitutions. In some examples, wherein n is greater than 1 , each R7 substituent may be independently selected from the above and may vary.In some examples, wherein n is greater than 1 , the R7 groups may be identical. In some examples, wherein n is greater than 1 , the R7 groups may be different.In some examples, q is 0 and hence the association of the at least one NMDA receptor agonist or a precursor thereof is at the five-membered pyrrole ring. In some examples, in which q is 0, the six-membered benzene ring may be substituted with at least one of R7, as shown below at times detailed as R3, R4, Rs or Re.In accordance with some aspects, the present disclosure provides a conjugate having a structure of Formula Ila:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K is a point of connectivity to at least one NMDA receptor modulator or a precursor thereof,Li is -(CH2)m-, -C(O)-, -O-, -NH-, -O-CH2-, -N-(CH2)m-, -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6,Ri and R2 are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, C1-C12 haloalkyl,R3, R4, Rs, Re is each independently from the other selected from hydrogen, deuterium, cyano, amino, amide, nitro, hydroxy, acetoxy, oxo, halo, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 haloalkenyl, C2-Ci2alkynyl, C2-C12 haloalkynyl, C1-C12 alkoxy, C1-C12 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, trifluoromethyl.In some examples, in which the psychedelic drug has an indole core as shown for example in the conjugate having a structure of Formula (Ila), the precursor thereof of apsychedelic drug has an indoline core as shown for example in the conjugate having a structure of Formula (lib).In accordance with some aspects, the present disclosure provides a conjugate having a structure of Formula lib:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K, Li, Ri and R2, R3, R4, Rs, and Re are as detailed above for Formula (Ila).In some examples, the substituent denoted as K in each one of the Formula provided herein is the point of connectivity to at least one NMDA receptor agonist or a precursor thereof. In some examples, the point of connectivity may be a covalent association.In some examples, the covalent association is a direct association between the indole or indoline core and the NMDA receptor agonist.In some examples, the covalent association is an indirect association between the indole or indoline core and the NMDA receptor agonist. In some examples, the covalent association between the indole or indoline core and the NMDA receptor agonist is via a linker. In some examples, the covalent association between the indole or indoline core and the NMDA receptor agonist is via a linker denoted herein at times as L2.In some examples, the NMDA receptor agonist or a precursor thereof is one or more of glutamate, Glycine, D-Serine, L-Aspartate, D-cycloserine, 1 -Aminocyclopropane- 1 -carboxylic acid (ACPC), Sarcosine, Rapastinel, a precursor thereof or any combinations thereof.In some examples, the NMDA receptor agonist or a precursor thereof is D-Serine, D- cycloserine, a precursor thereof or any combinations thereof.In some examples, the NMD A receptor agonist or a precursor thereof is D- Serine or a precursor thereof.In some examples, in which the NMDA receptor agonist is D-Serine, the precursor thereof of a NMDA receptor agonist comprises an oxazolidin-2-one moiety as shown for example in the conjugate having a structure of one or more of Formula (Illa), Formula (Illb), Formula (IVa), Formula (IVb), Formula (Va), Formula (Vb), Formula (Via), Formula (VIb), Formula (Vila), Formula (Vllb), Formula (Villa), Formula (Vlllb), Formula (IXa), Formula (IXb), Formula (Xa), Formula (Xb), Formula (Xia), Formula (Xlb), Formula (Xlla), Formula (Xllb), as shown herein. In some examples, in which the NMDA receptor agonist is D-Serine, the precursor thereof of a NMDA receptor agonist comprises an oxazolidin-2-one moiety as described herein, the precursor thereof is capable to undergo transformation (after cleavage) and form D-serine.In some examples, the NMDA receptor agonist or a precursor thereof is D -cycloserine or a precursor thereof.In some examples, in which the psychedelic drug has an indole core as shown for example in the conjugate having a structure of Formula (la), Formula (Ila), Formula (Illa), Formula (IVa), Formula (Va), Formula (Via), Formula (Vila), Formula (Villa), Formula (IXa), Formula (Xa), Formula (Xia), Formula (Xlla), a precursor thereof of a psychedelic drug has an indoline core as shown for example in the conjugate having a structure of Formula (lb), Formula (lib), Formula (Illb), Formula (IVb), Formula (Vb), Formula (VIb), Formula (Vllb), Formula (Vlllb), Formula (IXb), Formula (Xb), Formula (Xlb), Formula (Xllb), respectively as shown herein.In accordance with some aspects, the present disclosure provides a conjugate having a structure provided by Formula Illaor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri, R2, R3, R4, Rs, Re and Li are as defined above, L2 is -(CH2)t-, O-C(O), -C(O)-, -O-, -NH-, -O-CH2-, -N-(CH2)t-, or -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, t is selected from 0, 1, 2, 3, 4, 5 or 6.In accordance with some aspects, the present disclosure provides a conjugate having a structure provided by Formula Illbor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri, R2, R3, R4, Rs, Re, Li and L2 is as defined above.In some examples, in which the conjugate has the Formula (Illa) and / or (Illb), L2 is -C(=O)-.In some examples, the conjugate is provided by Formula IVaor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri, R2, R3, R4, Rs, Re and Li are as defined above.In some examples, the conjugate is provided by Formula IVbor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri, R2, R3, R4, Rs, Re and Li are as defined above.In some examples, Li is -(CH2)m-,-C(=0)-, -O-, -NH-, -O-CH2-, -N-(CH2)m-, -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6.In some examples, in which the conjugate is defined structure by Formula (la), Formula (lb), Formula (Ila), Formula (lib), Formula (Illa), Formula (Illb), Formula (IVa) or Formula (IVb), Li is -(CH2)m-, optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1 or 2.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (IVb), Li is -(CH2)2-, substituted with C1-C3 alkyl.In some examples, in which the conjugate is defined structure by Formula (la)-Formula (IVb), Li is -(CH2)2-, substituted with Ci alkyl.In some examples, in which the conjugate is defined structure by Formula (la)-Formula (IVb), Li is -(CH2)2-.In other embodiments, the conjugate is characterized by the structure of Formula Va:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof, wherein R1, R2, R3, R4, R5, R6are as described above.In some examples the conjugate has the following structure provided as Formula Vbor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof, wherein R1, R2, R3, R4, R5, R6are as described above.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vb), R3, R4, Rs, Re is each independently from the other selected from hydrogen, deuterium, hydroxy, acetoxy, C1-C12 alkyl, C1-C12 alkoxy. n some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vb), R3, R4, Rs, Re is each independently from the other selected from hydrogen, deuterium, hydroxy, acetoxy, Ci-Ce alkyl, Ci-Ce alkoxy.In still other embodiments, the conjugate is characterized by the structure of FormulaVia:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof, wherein R1, R2is H or Ci-Ce branched or straight chain alkyl and X if present is C1-C6 alkyl or halogen.In some examples the conjugate has the following structure provided as Formula (VIb)or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof, wherein R1, R2is H or Ci-Ce branched or straight chain alkyl and X if present is C1-C6 alkyl or halogen.In some examples the conjugate has the following structure provided as Formula Vila:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof, wherein R1, R2is H or Ci-Ce alkyl.In some examples the conjugate has the following structure provided as Formula Vllb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof, wherein R1, R2is H or Ci-Ce alkyl.In some examples, the conjugate is provided by a structure of Formula Villa:In some examples, the conjugate is provided by a structure of Formula Vlllb:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof, wherein R1, R2is H or Ci-Ce alkyl.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri and R2 are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, C1-C12 haloalkyl.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri and R2 are each H.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri and R2 are each Ci-Ce alkyl.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri and R2 are each Ci alkyl.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri and R2 are each C2 alkyl.I In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri and R2 are each C3 alkyl.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri is Ci alkyl and R2 is C2 alkyl.In some examples, in which the conjugate is defined structure by Formula (la) - Formula (Vlllb), Ri is Ci alkyl and R2 is C3 alkyl.In some examples, the conjugate has a structure provided by Formula IXa:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof.In some examples the conjugate has the following structure provided as Formula IXb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof.In some examples, the conjugate has a structure provided by Formula Xa:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof.In some examples, the conjugate has a structure provided by Formula Xb:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof.In some examples the conjugate has the following structure provided as Formula Xia:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or physiologically functional derivative thereof.The conjugate having the structure provided by Formula (Xia) is denoted herein as HBL20020.In some examples, the conjugate has the chemical formula 4-(3-(2- (diisopropylamino)ethyl)-4-hydroxy-lH-indole-l-carbonyl)oxazolidin-2-one.In some examples the conjugate has the following structure provided as Xlb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof.In some examples, the conjugate provided by Formula Xlb is denoted as HBL20021.In some examples, the conjugate has the chemical formula 4-(3-(2- (diisopropylamino)ethyl)-4-hydroxyindoline-l-carbonyl)oxazolidin-2-one.In some examples, the conjugate has a structure provided by Formula Xllaor a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof.In some examples, the conjugate has a structure provided by Formula Xllb:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or physiologically functional derivative thereof.In some examples, the conjugate denoted by HBL20020 comprises a precursor of a NMDA receptor modulator and a psychedelic drug. In some examples, the conjugate denoted by HBL20020 comprises a precursor thereof of a NMDA receptor agonist comprises an oxazolidin-2-one moiety.In accordance with some aspects, the conjugate is HBL20020 having a chemical formula 4-(3-(2-(diisopropylamino)ethyl)-4-hydroxy-lH-indole-l-carbonyl)oxazolidin-2-one.In some examples, the conjugate denoted by HBL20021 comprises a precursor of a NMDA receptor modulator and a precursor thereof of a psychedelic drug. In some examples, the conjugate denoted by HBL20021 comprises a precursor of a psychedelic drug having an indoline core and a precursor thereof of a NMDA receptor agonist comprises an oxazolidin-2- one moiety.In accordance with some aspects, the conjugate is HBL20021 having a chemical formula 4-(3-(2-(diisopropylamino)ethyl)-4-hydroxyindoline-l-carbonyl)oxazolidin-2-one.In accordance with some aspects, the conjugate has a structure of Formula XXa:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K is a point of connectivity to at least one NMDA receptor agonist or a precursor thereof, q is 0, 1, 2, 3, or 4,Li is -(CH2)m- ,-C(=0)-, -0-, -NH-, -O-CH2- -N-(CH2)m-, -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6, Ri and R2are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, Ci- C12 haloalkyl, R7 if present, is independently hydrogen, deuterium, cyano, amino, amide, nitro, hydroxy, acetoxy, oxo, halo, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 haloalkenyl, C2-C12 alkynyl, C2-C12 haloalkynyl, C1-C12 alkoxy, C1-C12 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, trifluoromethyl, n is selected from 0, 1, 2, 3, or 4.In accordance with some aspects, the conjugate has a structure of Formula XXb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K, q, Li, Ri, R2, R7 and n are as provided above for Formula (XXa).In some examples, in conjugates having structure (la) or (lb), q+n=4. In some examples, in conjugates having structure (XXa) or (XXb), q is 0 and n is 4. In some examples, in conjugates having structure (XXa) or (XXb), n is 0 and q is 4.It should be further noted that the substitution represented by R7 if present (namely in case n is not 0) may include one or more of the substitutions. In the structure, R7, where n is greater than 1 , each R7 substituent may be independently selected and can vary, meaning the R7 groups do not need to be identical for all occurrences.In some examples, in which the conjugate is defined structure by Formula (XXa), or Formula (XXb), R7 if present, is independently hydrogen, deuterium, hydroxy, acetoxy, C1-C12 alkyl, C1-C12 alkoxy. In some examples, in which the conjugate is defined structure by (XXa), or Formula (XXb), n is selected from 0, 1, 2, 3, or 4.In some examples, in which the conjugate is defined structure by (XXa), or Formula (XXb), R7 is hydrogen and n=3.In some examples, the substituent denoted as K in conjugates of (XXa), or Formula (XXb), is the point of connectivity to at least one NMD A receptor agonist or a precursor thereof. In some examples, the point of connectivity may be a covalent association.In some examples, the covalent association is a direct association between the indole and the NMDA receptor agonist. In some examples, the covalent association is an indirect association between the indole and the NMDA receptor agonist.In some examples, the covalent association between the indole core and the NMDA receptor agonist is via a linker.In some examples, the covalent association between the indole core and the NMDA receptor agonist is via a linker denoted herein at times as L2.In some examples, in which the psychedelic drug has an indole core as shown for example in the conjugate having a structure of Formula (XXa), (XXIa) the precursor thereof of a psychedelic drug has an indoline core as shown for example in the conjugate having a structure of Formula (XXb), (XXIb).In some examples, the NMDA receptor agonist or a precursor thereof is one or more of glutamate, Glycine, D-Serine, L-Aspartate, D-cycloserine, 1 -Aminocyclopropane- 1 -carboxylic acid (ACPC), Sarcosine, Rapastinel, a precursor thereof or any combinations thereof. In some examples, the NMDA receptor agonist or a precursor thereof is D-Serine, D-cycloserine, a precursor thereof or any combinations thereof. In some examples, the NMDA receptor agonist or a precursor thereof is D-serine or a precursor thereof. In some examples, the NMDA receptor agonist or a precursor thereof is D-cycloserine or a precursor thereof.In accordance with some aspects, the conjugate has a structure of Formula XXIaor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri and R2, Li, R7 and n are as defined above, L2 is -(CH2)t-, -O-C(=O)-, -C(=O), -O-, -NH-, -O-CH2-, -N-(CH2)t-, or - NH-C(=O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, t is selected from 0, 1, 2, 3, 4, 5 or 6.In accordance with some aspects, the conjugate has a structure of Formula XXIbor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri, R2, Li, R7, L2, n are as defined above.In some examples, in the conjugate having Formula (XXa), Formula (XXb), Formula (XXIa), Formula (XXIb), L2is -C(=O)-, -(CEbjt- or -O-C(=O)-, t is selected from 0, 1, 2, 3, 4, 5 or 6. In some examples, in the conjugate having Formula (XXa), Formula (XXb), Formula (XXIa), Formula (XXIb), L2is -O-C(=O)-.In accordance with some examples, the conjugate has a structure of Formula XXIIaor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri and R2, Li, R7 and n are as defined above.In accordance with some examples, the conjugate has a structure of Formula XXIIbor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri and R2, Li, R7 and n are as defined above.In some examples, R7 if present, is independently hydrogen, deuterium, hydroxy, acetoxy, C1-C12 alkoxy. In some examples, in which n=3 and R7 is the same or different selected from hydrogen, deuterium, hydroxy, acetoxy, C1-C12 alkoxy.In some examples, in which the conjugate is defined structure by Formula (XXa) - Formula (XXIIb), Li is -(CH2)m-, optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1 or 2.In some examples, in which the conjugate is defined structure by Formula (XXa) - Formula (XXIIb), Li is -(CH2)2-.In some examples, in which the conjugate is defined structure by Formula (XXa) - Formula (XXIIb), Li is -(CH2)2-, substituted with C1-C3 alkyl.In some examples, in which the conjugate is defined structure by In some examples, in which the conjugate is defined structure by Formula (XXa) -Formula (XXIIb), Li is -(CH2)2-, substituted with Ci alkyl.In accordance with some examples, the conjugate has a structure of Formula XXIIIaor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof wherein Ri and R2, are as defined above.In accordance with some examples, the conjugate has a structure of Formula XXIIIbor a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof wherein Ri and R2, are as defined above.In some examples, in which the conjugate is defined structure by Formula (XXa), - Formula (XXIIb), Ri and R2 are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, C1-C12 haloalkyl.In some embodiments, the conjugate is characterized by the structure of Formula XXIVa or Formula XXI Vb:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or a physiologically functional derivative thereof wherein Ri, R2 is H or Ci-Ce branched or straight chain alkyl and X if present is Ci-Ce alkyl or halogen.In some embodiments, the conjugate is characterized by the structure of Formula XXVa or XX Vb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof wherein Ri and R2, are as defined above.In some embodiments, the conjugate is characterized by the structure of Formula XX Va’ or XX Vb’or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or a physiologically functional derivative thereof wherein Ri and R2, are as defined above.In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri and R2 are each H.In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri and R2 are each Ci-Ce alkyl.In some examples, in which the conjugate is defined structure by In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri and R2 are each Ci alkyl.In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri and R2 are each C2 alkyl.In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri and R2 are each C3 alkyl.I In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri is Ci alkyl and R2 are each C2 alkyl.In some examples, in which the conjugate is defined structure by (XXa)-Formula (XXVb’), Ri is Ci alkyl and R2 are each C3 alkyl.In some embodiments, the conjugate is characterized by the structure of Formula XX Via or XXVIb:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or a physiologically functional derivative thereof.In some embodiments, the conjugate is characterized by the structure of FormulaXX Vila or XXVIIb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof.In some embodiments, the conjugate is characterized by the structure of Formula XXVIIc or XXVIIdIn some examples, the conjugate having Formula XXVIIc is denoted herein as HBL20018.In some examples, the conjugate has the chemical formula 3-(2- (diisopropylamino)ethyl)-lH-indol-4-yl (3-oxoisoxazolidin-4-yl)carbamate.In accordance with some aspects, the conjugate is HBL20018 having the chemical formula 3-(2-(diisopropylamino)ethyl)-lH-indol-4-yl (3-oxoisoxazolidin-4-yl)carbamate.It should be noted that the conjugates provided by the above Formulas may encompass any enantiomer thereof and preferably, a D-enantiomer of the NMD AR agonist, a D-enantiomer of the NMDAR agonist precursor. In some examples, the conjugate comprises D-Serine, D- Serine precursor, D-cyloserine, D-cyloserine precursor or any combination thereof.In some aspects, the invention relates to conjugates that cab be specifically cleaved in situ, in nervous tissue, for example, upon crossing the blood-brain barrier (BBB), whereupon cleavage at specific sites occurs to release two active components of the conjugates.In some aspects, for example, with regard to conjugates provided herein above, metabolic scission may occur in site, releasing 4-HO-DiPT or precursor thereof and further releasing the NMDAR agonist or precursor thereof, such that the 4-HO-DiPT precursor undergoes conversion to 4-HO-DiPT in situ.In some aspects, for example, with regard to conjugates provided herein above,metabolic scission may occur in site, releasing 4-HO-DiPT or precursor thereof and further releasing the NMDAR agonist or precursor thereof, such that the NMD AR agonist precursor undergoes conversion to D-Serine in situ.In other aspects, for example, with regard to the conjugates provided herein above, scission releases 4-HO-DiPT and D-cyloserine after decarboxylation occurs, in situ, releasing the two active components from the conjugate.In some aspects, the invention specifically contemplates use of conjugates with dual action to modulate the function of NMDA receptors in the cortex and other brain areas in combination with psychedelics and / or agents modulating 5-HT2A receptor function and in some embodiments, it is specifically contemplated to use agents modulating 5-HT2A receptor function and psychedelics for their effect on treating schizophrenia and other neuropsychiatric diseases.In some embodiments, the invention further provides a composition comprising any conjugate of this invention, including in any embodied description of the conjugate as herein provided.A further aspect of the present disclosure relates to a composition comprising the conjugate described herein, the composition optionally further comprises at least one of pharmaceutically acceptable carrier / s, excipient / s, auxiliaries, and / or diluent / s.In some embodiments, the composition is a pharmaceutical composition.The pharmaceutical compositions of the invention can be administered and dosed by the methods of the invention, in accordance with good medical practice, systemically, for example intravenously. It should be noted however that the invention may further encompass additional administration modes. In other examples, the pharmaceutical composition can be introduced to a site by any suitable route including oral, intranasal, or intraocular administration, intraperitoneal, subcutaneous, transcutaneous, topical, intramuscular, intraarticular, subconjunctival, or mucosal.In yet some further embodiments, the composition of the invention may optionally further comprise at least one of pharmaceutically acceptable carrier / s, excipient / s, additive / s diluent / s and adjuvant / s. More specifically, pharmaceutical compositions used to treat subjects in need thereof according to the invention, which may conveniently be presented in unit dosage form, may be prepared according to conventional techniques well known in the pharmaceuticalindustry. Such techniques include the step of bringing into association the active ingredients with the pharmaceutical carrier(s) or excipient(s). In general formulations are prepared by uniformly and intimately bringing into association the active ingredients, specifically, the compound of the invention with liquid carriers or finely divided solid carriers or both, and then, if necessary, shaping the product. The compositions may be formulated into any of many possible dosage forms such as, but not limited to, tablets, capsules, liquid syrups, soft gels, suppositories, and enemas. The compositions of the present invention may also be formulated as suspensions in aqueous, non-aqueous or mixed media. Aqueous suspensions may further contain substances which increase the viscosity of the suspension including, for example, sodium carboxymethylcellulose, sorbitol and / or dextran. The suspension may also contain stabilizers. The pharmaceutical compositions of the present invention also include, but are not limited to, emulsions and liposome-containing formulations. It should be understood that in addition to the ingredients particularly mentioned above, the formulations may also include other agents conventional in the art having regard to the type of formulation in question.The pharmaceutical compositions of the invention can be administered at frequency and by the methods of the invention, in accordance with good medical practice depending on the clinical presentation of the subject in need. In some embodiments, the conjugate may be administered as frequently as once a week to once a month, and the skilled clinician will know how to adjust the frequency of administration depending on the clinical presentation of the subject in need.In some other embodiments, the conjugate may be administered on a daily or essentially daily basis for from 1 to 4 weeks. Daily administration is also intended to include the possibility of alternate day dosing as well as 3 times, twice or once weekly administrations, as will be appreciated by the skilled artisan.As shown in Example 2, a decrease in HTR was observed. Based on the results shown herein, it was suggested that the compounds of the present disclosure may be suitable for treating disease or disorders mediated by one or more serotonergic receptors in which attenation of the psychedelic trip (represented in mice by reduced HTR) would be advantageous.In some aspects of the invention, the conjugate of the present disclosure and / or the compositions comprising the same are for use in a method of treating a disease that would benefit from administration of the conjugates described herein.Hence, in accordance with some aspects, the present disclosure provides a conjugate or a composition comprising the conjugate for use in treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a disease associated with brain function.In some examples, the disease associated with brain function comprises a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof.In accordance with some aspects, the present disclosure provides a conjugate or a composition comprising the conjugate for use in in treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder.In another aspect, the present disclosure provides a method for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in a subject in need thereof. The method comprises in some embodiments the step of administering to the subject a therapeutically effective amount of the conjugate comprising at least one psychedelic compound or a precursor thereof and at least one N-methyl D-aspartate (NMDA) receptor (NMD AR) modulator or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a a brain disease in a subject in need thereof, comprises at least one 5-HT2A receptor modulator or a precursor thereof and at least one NMD AR agonist or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof, comprises at least one 5-HT2A receptor modulator or a precursor thereof and at least one NMD AR agonist or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof, comprises 4-HO-DiPT or a precursor thereof and D-serine or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof, comprises 4-HO-DiPT or a precursor thereof and D-cycloserine or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof, is provided by one or more the Formulas provided herein.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof is HBL20020. In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof is HBL20021. In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a brain disease in a subject in need thereof is HBL20018.In a further aspect, the present disclosure provides a method for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of at least one brain disorder or a brain disease in a subject in need thereof. The method comprising administering to the subject a therapeutically effective amount of the conjugate.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in a subject in need thereof, comprises at least one psychedelic compound or a precursor thereof and at least one NMD AR modulator or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in asubject in need thereof, comprises at least one 5-HT2A receptor modulator or a precursor thereof and at least one NMD AR agonist or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in a subject in need thereof, comprises 4-HO-DiPT or a precursor thereof and D-serine or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in a subject in need thereof, comprises 4-HO-DiPT or a precursor thereof and D-cycloserine or a precursor thereof.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in a subject in need thereof, is provided by one or more of the Formulas described herein.In some embodiments, which can be considered as aspects of the present disclosure, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of a neuropsychiatric disease, a neurocognitive disease, a neurologic disease, a motor disease or any combination thereof in a subject in need thereof, is HBL20020, HBL20021 or HB20018.A neuropsychiatric disease refers to a condition that involves both neurological and psychiatric symptoms and result from dysfunctions in the brain’s structure or function, affecting behavior, emotion regulation, cognition, and mood, typically associated with mood and behavior.In some examples, the neuropsychiatric disease is one or more of major depressive disorder (depression), bipolar disorder, schizophrenia, generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), attention- deficit / hyperactivity disorder (ADHD), panic disorder, anxiety disorder [these two were addedfrom the first provisional]. In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of OCD.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of an anxiety disorder.In some examples, the disease is substance abuse.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of ADHD.As used herein, “Attention-deficit hyperactivity disorder” (ADHD) is a mental disorder of the neurodevelopmental type characterized by one or more of inattention, hyperactivity, and impulsivity, which are otherwise not appropriate for a person's age. It is commonly diagnosed in childhood and is one of the most frequent condition affecting school-aged children. In children, the primary symptoms of inattention, hyperactivity, and impulsivity can lead to disruptive behavior at home and in school, which is a typical precursor to clinical referral for diagnosis and treatment. Hyperactivity often decreases in adulthood; however inattention, disorganization, and impulsivity typically persist, causing functional challenges to the patient on a day-to-day basis.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of schizophrenia.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of treatment-resistant schizophrenia.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of PTSD.A neurologic disease refers to a condition that primarily affects the nervous system (the brain, spinal cord, and peripheral nerves).In some examples, the neurologic disease is one or more of epilepsy, stroke, multiplesclerosis, amyotrophic lateral sclerosis (ALS), and Parkinson’s disease.In some examples, the neurologic disease is amyotrophic lateral sclerosis (ALS).In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of ALS.ALS as used herein refers to a progressive neurodegenerative disease. ALS is also known as Motor Neuron Disease (MND), Lou Gehrig's Disease, and Charcot's disease. It should be noted that when reefing to ALS this encompasses sign or symptom of ALS. In some embodiments, the sign or symptom of ALS is muscle twitching, muscle weakness, muscle stiffness, difficulty speaking, difficulty swallowing, difficulty breathing, cognitive impairment, or pain.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of Multiple sclerosis (MS). MS as used herein refers to a clinically isolated syndrome (CIS). In some embodiments, the MS is relapsing-remitting MS (RRMS). In some embodiments, the MS is primary progressive MS (PPMS). In some embodiments, the MS is secondary progressive MS (SPMS). In some embodiments, the improved sign or symptom of MS can include a neurological symptom or sign, such as an autonomic, visual, motor, or sensory problem. In some embodiments, the improved sign or symptom of MS can include double vision, blindness in one eye, muscle weakness, trouble with sensation, trouble with coordination, loss of sensitivity, changes in sensation such as tingling, pins and needles or numbness, muscle weakness, blurred vision, very pronounced reflexes, muscle spasms, or difficulty in moving; difficulties with coordination and balance (ataxia); problems with speech or swallowing, visual problems (nystagmus, optic neuritis or double vision), feeling tired, acute or chronic pain, and bladder and bowel difficulties (such as neurogenic bladder). In some embodiments, the improved sign or symptom of MS can include difficulties thinking and emotional problems such as depression or unstable mood. In some embodiments, the improved sign or symptom of MS can include a reduction or decrease in Uhthoffs phenomenon, a worsening of symptoms due to exposure to higher than usual temperatures, and Lhermitte's sign, an electrical sensation that runs down the back when bending the neck. In some embodiments, after administration of psilocybin a subject demonstrates an improvement in their expanded disability status scale (EDSS) and / or multiple sclerosis functional composite score.In some embodiments, the conjugate applicable by the methods of the present disclosure for treating, preventing, inhibiting, reducing, eliminating, protecting or delaying the onset of epilepsy.In some embodiments, the epilepsy is generalized epilepsy, epilepsy with myoclonic absence seizures, focal epilepsy, generalized and focal epilepsy, unknown if generalized or focal epilepsy, autosomal dominant nocturnal frontal lobe epilepsy, childhood absence epilepsy, benign rolandic epilepsy, Doose syndrome, Dravet syndrome, early myoclonic encephalopathy, Jeavons syndrome, epilepsy in infancy with migrating focal seizures, epileptic encephalopathy with continuous spike and wave during sleep, febrile illness-related epilepsy syndrome, frontal lobe epilepsy, west syndrome, juvenile absence epilepsy, juvenile myoclonic epilepsy, Landau- Kleffner syndrome, Lennox-Gastaut syndrome, Ohtahara syndrome, Panayiotopoulos syndrome, progressive myoclonic epilepsy, reflex epilepsy, or temporal lobe epilepsy. In some embodiments, the subject in need thereof has generalized tonic-clonic, convulsive, absence, myoclonic, clonic, tonic, or atonic seizures.A neurocognitive disease is characterized by a decline in cognitive function typically due to damage or dysfunction in the brain.In some examples, the neurocognitive disease is one or more of Alzheimer’s disease, vascular dementia, Lewy body dementia, and frontotemporal dementia.In some embodiments, the term “neurocognitive disorder” refers to a wide range of disorders that affect the brain, and are often associated with decreased or altered mental function.In some embodiments, the neurocognitive disorder is a major neurocognitive disorder. In some embodiments, the neurocognitive disorder is mild neurocognitive disorder.In some embodiments, the neurocognitive disorder is dementia. In some embodiments, the dementia is late onset dementia (with or without hallucinations), hallucinations co-occurrent and due to late onset dementia; mild dementia; mixed dementia; moderate dementia; organic dementia; presbyophenia; presbyophrenic psychosis; presenile dementia; presenile dementia with delirium; presenile dementia with depression, presenile dementia with delusions; primary degenerative dementia; senile dementia; senile dementia with delusions; senile dementia with delirium, depression, paranoia, or psychosis; or severe dementia.In some embodiments, the neurocognitive disorder is caused by traumatic brain injury, such as bleeding into the brain (intracerebral hemorrhage), bleeding into the space around thebrain (subarachnoid hemorrhage), blood clot inside the skull causing pressure on brain (subdural or epidural hematoma), or concussion.In some embodiments, the neurocognitive disorder is caused by a breathing condition, such as low oxygen in the body (hypoxia) or high carbon dioxide level in the body (hypercapnia).In some embodiments, the neurocognitive disorder is caused by a cardiovascular disorder, such as dementia due to many strokes (multi-infarct dementia), heart infections (endocarditis, myocarditis), stroke, or transient ischemic attack (TIA).In some embodiments, the neurocognitive disorder is caused by a degenerative disorder, such as Alzheimer's disease (also called senile dementia, Alzheimer type), Creutzfeldt-Jakob disease, Diffuse Lewy body disease, Huntington's disease, Multiple sclerosis, Normal pressure hydrocephalus, Parkinson's disease, or Pick disease. In some embodiments, the neurocognitive disorder is due to one or more of Alzheimer's disease, Lewy Body Dementia, Traumatic Brain Injury, Prion Disease, HIV Infection, Parkinson's disease, or Huntington's disease.In some embodiments, the neurocognitive disorder is dementia due to metabolic causes, such as kidney disease, liver disease, thyroid disease (hyperthyroidism or hypothyroidism), or vitamin deficiency (Bl, Bl 2, or folate).In some embodiments, the neurocognitive disorder is caused by a drug or alcohol-related condition, such as alcohol withdrawal state, intoxication from drug or alcohol use, Wernicke- Korsakoff syndrome (a long-term effect of excessive alcohol consumption or malnutrition), or withdrawal from drugs (such as sedative-hypnotics and corticosteroids).In some embodiments, the neurocognitive disorder is caused by an infection, such has any sudden onset (acute) or long-term (chronic) infection. For example, the infection may be blood poisoning (septicemia), brain infection (encephalitis), meningitis (infection of the lining of the brain and spinal cord), prion infections (e.g., mad cow disease), or late-stage syphilis.In some embodiments, the neurocognitive disorder is caused by complications from cancer and / or cancer treatment with chemotherapy.In some embodiments, the neurocognitive disorder is caused by depression, neurosis, or psychosis.In some embodiments, the neurocognitive disorder is mild cognitive impairment.In some embodiments, the subject has one or more diseases, disorders, or conditions that are comorbid with the neurocognitive disorder. For example, the one or more comorbidities may be hypertension, connective tissue disease, depression, diabetes, or chronic pulmonary disease.In some embodiments, the neurocognitive disorder is due to Alzheimer's disease (AD), such as sporadic Alzheimer's Disease or Familial Alzheimer's Disease.A motor disease typically involves abnormalities in movement or motor control.In some examples, the motor disease is one or more of Parkinson’s disease, Parkinsonian syndrome, Huntington’s disease, cerebral palsy, and essential tremor.In some embodiments, the Parkinsonian syndrome is Parkinson's disease. In some embodiments, the Parkinsonian syndrome is drug-induced.In some embodiments, the Parkinsonian syndrome is an atypical Parkinsonian disorder. In some embodiments, the atypical parkinsonian disorder is multiple system atrophy progressive supranuclear palsy, corticobasal degeneration, or dementia with Lewy bodies.In some embodiments, the subject suffers from a motor symptom or a nonmotor symptom, or combinations thereof. In some embodiments, the motor symptom is bradykinesia, rigidity, tremor, rest tremor, postural instability, stiffness, slowness, imbalance, or combinations thereof. In some embodiments, the nonmotor symptom is cognitive impairment, olfactory loss, sleep dysfunction, autonomic dysfunction, psychiatric disturbance, fatigue, softening of the voice, sialorrhea, trouble swallowing, or combinations thereof.In some embodiments, the subject has one or more diseases, disorders, or conditions that are comorbid with a Parkinsonian syndrome. In some embodiments, the comorbidity results from a symptom of a Parkinsonian syndrome. In some embodiments, the comorbidity is selected from a neuropsychiatric disturbance, a sleep disorder, melanoma, neurogenic orthostatic hypotension, pseudobulbar affect, anemia, hypertension, type 2 diabetes, restless leg syndrome, cancer, or combinations thereof. In some embodiments, the comorbidity is a neuropsychiatric disturbance, and wherein the neuropsychiatric disturbance is dementia, depression, psychosis, apathy, anxiety, hallucinations, or combinations thereof. In some embodiments, comorbidity is a sleep disorder (e.g., rapid eye movement sleep behavior disorder), and wherein the sleep disorder is daytime drowsiness and sleepiness, sleep attacks, insomnia, or rapid eye movement sleep behavior disorder.According to this aspect, and in some embodiments, the invention contemplates, when treating a Parkinsonian syndrome or symptom thereof in a subject in need thereof further administering to the subject at least one additional therapy. In some embodiments, the additional therapy is exercise, physical, occupational, or speech therapy. In some embodiments, the additional therapy is a dopaminergic medication. In some embodiments, the additional therapy is carbidopa-levodopa, entacopone, tolcapone, carbidopa, levodopa entacapone, pramipexole, ropinirol, apomorphine, rotigotine, selegiline, rasagiline, safinamide, amantadine, istradefylline, trihexyphenidyl, benztropine / benzatropine, or combinations thereof.In some embodiments, the methods for treating a Parkinsonian syndrome or symptom thereof described herein ameliorate the Parkinsonian syndrome, or at least one symptom thereof, in the subject.In some aspects, the disease or disorder is one or more of schizophrenia, depression, post-traumatic stress disorder, obsessive-compulsive disorder (OCD), cerebral palsy, muscular dystrophy, spina bifida, spinal muscle atrophy (SMA), Parkinson's disease, epilepsy, amyotrophic lateral sclerosis (ALS), Ataxia, attention-deficit hyperactivity disorder, generalized anxiety disorder, or panic disorder, cervical dystonia, general dystonia, chorea, functional movement disorder, Huntington's disease, multiple system atrophy, myoclonus, chronic pain, inflammation, Parkinsonism, Alzheimer’s disease, sleep-wake disorders, stroke or repeated head trauma, progressive supranuclear palsy, restless legs syndrome, tardive dyskinesia, Tourette syndrome, tremor, or Wilson's disease or an autism spectrum disorder (ASD) or a symptom thereof, or any related disorder as herein described.In some embodiments, the disease or disorder is pain and / or chronic pain.As used herein, the term “chronic pain” refers to pain that lasts longer than the usual course of an acute injury or disease, such as pain that recurs for months or years. “Nociceptive pain” is a high-threshold pain activated in the presence of intense stimuli, such as touching something too hot, cold, or sharp. It minimizes contact with harmful stimuli and demands immediate action and attention. “Neuropathic pain” is a chronic pain caused by lesion or disease of the somatosensory system and can lead to altered transmission of sensory signals to the spinal cord and brain. Conditions associated with neuropathic pain include multiple sclerosis, diabetic neuropathy, post-herpetic neuralgia, brachial plexus injury, allodynia, human immunodeficiency virus (HIV) infection, amputation, nerve injury pain, stroke, cancer-related pain, trigeminal neuralgia, central neuropathic pain, post-traumatic neuropathy, postsurgical neuropathy,cervical and lumbar polyradiculopathies, leprosy, autoimmune disorders, inflammatory disorders, channelopathies and metabolic disorders. Additional examples of types of pain include visceral pain and bone pain.In some embodiments, the disease or disorder is inflammation.In some embodiments, disease or disorder is stroke. In some embodiments, the stroke is an ischemic stroke, or a hemorrhagic stroke.When referring to stroke it should be understood that it encompasses sign or symptom of stroke. The sign or symptom of stroke may be, for example, paralysis, numbness or weakness in the arm, face, or leg, trouble speaking or understanding speech, confusion, slurring speech, vision problems, trouble walking, loss of balance or coordination, dizziness, or headache. In some embodiments, the sign or symptom of stroke is improved within 1 hour of administration. In some embodiments, the sign or symptom of stroke is improved within 12 hours of administration. In some embodiments, the sign or symptom of stroke is improved for a period of at least 1 month after administration. In some embodiments, the sign or symptom of stroke is improved for a period of at least 3 months after administration. In some embodiments, the sign or symptom of stroke is improved for a period of at least 12 months after administration.In some embodiment, the disease is one or more of oppositional defiant disorder, learning difficulties, depression, anxiety, bipolar disorder, substance use disorders, autism spectrum disorders, personality disorder, obsessive compulsive disorder, or combinations thereof.In some embodiments, the disease is migraine and / or cerebrovascular disease.In some embodiment, the disease is Autism or Autism spectrum disorder (ASD). Autism spectrum disorder (ASD) is a neurodevelopmental syndrome characterized by core deficits in social interaction and communication, presence of repetitive and restricted patterns of behavior and interests, and / or unusual reactivity to sensory input. In some embodiments, the ASD is autistic disorder, Asperger's syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), childhood disintegrative disorder, or combinations thereof. In some embodiments, the sign or symptom of ASD is irritability, repetitive behavior, restricted behaviors, unusual reactivity to sensory stimuli, social communication deficits, aggression, self- injurious behavior, motor impairment, cognitive deficits, or combinations thereof. In some embodiments, the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), Autism Diagnostic Interview-Revised (ADI-R), Childhood Autism Rating Scale, Second Edition (CARS2), Vineland-II Adaptive Behavior Scales (VABS-2), Aberrant Behavior Checklist(ABC), Child Behavior Checklist (CBCL), Autism Behavior Inventory (ABI), Social Responsiveness Scale, Second Edition (SRS-2), Repetitive Behavior Scale-Revised (RBS-R), the Ohio Autism Clinical Impressions Scale-Improvement (OACIS-I), Ohio Autism Clinical Impressions Scale-Severity (OACIS-S), the Gilliam Autism Rating Scale-Third Edition (GARS- 3), Social Communication Questionnaire (SCQ), Autism Spectrum Quotient (AQ), Adult Repetitive Behavior Questionnaire-2 (RBQ-2A), or combinations thereof, are used to assess the efficacy of treating according to the methods of the disclosure.In some embodiments, the subject suffers from cognitive deficits in cognitive flexibility, sustained attention, working memory, episodic memory, executive function, or combinations thereof.In some embodiments, disease or disorder is anxiety disorders, sleep-wake disorder, impulse-control, disruptive behavior, conduct disorder, depressive disorders, obsessive- compulsive and related disorders, bipolar disorder, schizophrenia, or combinations thereof. In some embodiments, the comorbidity is an inflammatory disorder, gastrointestinal disorder, epilepsy, or a combination thereof.In some embodiment, the disease or disorder is a sleep-wake disorder.Sleep-wake disorders are a class of diseases or disorders including insomnia disorder, hypersomnolence disorder, narcolepsy, breathing-related sleep disorders (such as central sleep apnea), circadian rhythm sleep-wake disorders, non-rapid eye movement sleep arousal disorders, nightmare disorder, rapid eye movement sleep behavior disorder, restless leg syndrome, and substance / medication-induced sleep disorder. Individuals with these disorders typically present with sleep-wake complaints of dissatisfaction regarding the quality, timing, and amount of sleep, which often results in daytime distress. As used herein, the term insomnia refers to an individual's difficulty with sleep.In some embodiments, the subject has excessive daytime sleepiness, cataplexy, sleep paralysis, hypnagogic hallucinations, hypnopompic hallucinations, or combinations thereof prior to treatment with psilocybin or an active metabolite thereof.In some embodiments, the subject has one or more diseases, disorders, or conditions that are comorbid with a sleep-wake disorder. For example, the subject may have one or more of mood disorders, affective disorders, neurodegenerative disorders, neurode velopmental disorders, autism spectrum disorders, and substance abuse disorders. In some embodiments, the subject has major depressive disorder, mania, depression, anxiety, psychosis, attention deficithyperactivity disorder (ADHD), Parkinson's disorder, autism spectrum disorder (ASD), panic attacks, one or more social phobias, one or more eating disorders, and / or schizophrenia.The regimen of administration may affect what constitutes an effective amount. The therapeutic formulations may be administered to the subject either prior to or after the onset of a neurological disease or disorder or a disease or disorder that is affected by, associated with, or would benefit from conjugates as described herein.According to this aspect and in some embodiment, the conjugates / compositions / methods / uses cause a demonstrated improvement in one or more of the following: the MiniMental State Exam (MMSE), the Mini-Cog test, a CANTAB test, a Cognigram test, a Cognivue test, a Cognition test, or an Automated Neuropsychological Assessment Metrics test, EEG cognition-related parameters.In some embodiment, the disease or disorder is as described in US2009203750, WO- 2022067165, US11254640, EP3519816, WO-2021076572 or WO-2020176599, which are hereby incorporated by reference in their entirety.The present disclosure encompasses the conjugates or the compositions comprising the same for use with one or more additional therapeutic agent.The selection of the additional therapeutic agent may vary based on the specific indication to be treated, allowing for tailored therapeutic strategies that address distinct clinical needs. This combinatorial approach provides flexibility in therapeutic application, where the conjugates may enhance efficacy or complement the mechanisms of action of the additional agent, thereby offering potential for improved patient outcomes across multiple indications.In some examples, the one or more additional therapeutic agent may be an antidepressant, cholinesterase inhibitors, AChE (acetylcholinesterase) inhibitor, BChE (Butyrylcholinesterase) inhibitor, NMDA (N-methyl-D-aspartate) antagonist, or combinations thereof. A non-limiting list of exemplary types of antidepressants includes: SSRIs (selective serotonin reuptake inhibitors), MAOIs (monoamine oxidase inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors), and TCAs (tricyclic antidepressants). For example, the antidepressant may be citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine, vilazodone, duloxetine, venlafaxine, desvenlafazine, levomilnacipran, amitriptyline, amoxapine, clomipramine, desipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine, mirtazapine, bupropion, trazodone, vortioxetine, or vilazodone.In some embodiments, the additional therapeutic agent is a stimulant, a norepinephrine reuptake inhibitor, an a-adrenergic agonist, a tricyclic antidepressant, modafinil, or combinations thereof. In some embodiments, the additional therapeutic agent is a stimulant (e.g., an amphetamine or methylphenidate). In some embodiments, the additional therapeutic agent is a norepinephrine reuptake inhibitor (e.g., atomoxetine or reboxetine).In some embodiments, the additional therapeutic agent is a sodium channel blocker, calcium current inhibitor, gamma-aminobutyric (GABA) enhancer, glutamate receptor antagonists, carbonic anhydrase inhibitor, hormone, an N-methyl-D-aspartate (NMD A) receptor antagonist, synaptic vesicle glycoprotein 2A (SV2A) ligand, a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) / Kainate receptor antagonist, or combinations thereof. In some embodiments, the additional therapeutic agent is a sodium channel blocker, and the sodium channel blocker is phenytoin, fosphenytoin, carbamazepine, lamotrigine, or valproate. In some embodiments, the additional therapeutic agent is a calcium channel antagonist, and wherein the calcium current inhibitor is ethosuximide or valproate. In some embodiments, the additional therapeutic agent is a GABA enhancer, and wherein the GABA enhancer is a benzodiazepine, barbiturate, progabide, progesterone, ganaxolone, vigabatrin, tiagabine, gabapentin, or valproate.In some embodiments, the least one additional therapeutic agent is risperidione or aripiprazole. In some embodiments, the at least one additional therapeutic agent is an antidepressant, such as SSRIs (selective serotonin reuptake inhibitors), MAOIs (monoamine oxidase inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors), and TCAs (tricyclic antidepressants). For example, the antidepressant may be citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, vortioxetine, vilazodone, duloxetine, venlafaxine, des venlaf azine, levomilnacipran, amitriptyline, amoxapine, clomipramine, desipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, trimipramine, mirtazapine, bupropion, trazodone, vortioxetine, or vilazodone,In some embodiments, the least one additional therapeutic agent is D- amino acid oxidase (DAAO) inhibitors, such as, for example luvadaxistat, benzoic acid, pyrrole-2-carboxylic acids, and indole-2-carboxylic acids, for example as described in EP 396124, WO 03 / 039540 WO / 2005 / 089753, or the compounds AS057278 (5-methylpyrazole-3-carboxylic acid) (Adage, T. et al., Eur Neuropsychopharmacol 2008, 18 (3), 200-14), CBIO (6-chlorobenzo[d]isoxazol- 3-ol) (Ferraris, D. et al., J Med Chem 2008, 51 (12), 3357-9) and 4H-thieno [3,2-b] pyrrole-5-carboxylic acid from Merck (Smith, S. M. et al., J Pharmacol Exp Ther 2009, 328 (3), 921-30), 3-hydroxyquinolin-2-(lH)-one, benzo[d]61soxazole-3-ol core and others as will be known to the skilled artisan.In some embodiments, the least one additional therapeutic agent is an alanine-serine- cysteine transporter inhibitor, a D-amino acid oxidase inhibitor, a glycine transport inhibitor or a combination thereof as an additional therapeutic agent, as herein described.In some embodiments, the at least one additional therapeutic agent is interferon beta- la, interferon beta-lb, glatiramer acetate, mitoxantrone, natalizumab, fingolimod, teriflunomide, dimethyl fumarate, alemtuzumab, ocrelizumab, siponimod, cladribine, and ozanimod.In some embodiments, the at least one additional therapeutic agent is an anti-platelet drug (e.g., aspirin) or an anti-coagulant (e.g., warfarin, dabigatran, rivaroxaban, apizaban, edoxaban).In some embodiments, the at least one additional therapeutic agent is psilocin.In some embodiments, the at least one additional therapeutic agent is a tricyclic antidepressant or a serotonin-noradrenaline reuptake inhibitor (SNRI). In some embodiments, the at least one additional therapeutic is pregabalin or gabapentin. In some embodiments, the at least one additional therapeutic is lidocaine, capsaicin, tramadol, botulinum toxin A, oxycodone, morphine, fentanyl, a cannabinoid, ketamine, acetaminophen, a nonsteroidial anti-inflammatory drug, an opioid, calcitonin,The conjugate or composition as described herein may be administered prior to, proximal to, or coincident with the additional therapeutics, for example adjunct psychotherapy.The conjugates, compositions and / or additional therapeutics may be administered by doses effective to treat the required disease, disorder or condition.In some examples, in which the conjugate or method comprise administration of D-serine or any precursor thereof, the D-serine or any precursor thereof may be at a dosage of 1.5 grams- 15 grams as a daily or bolus dosage administration, at times between 5-15 grams / day, at times between 1.5 - 7 grams / day, at times between 3 - 10 grams / day, at times 5 - 15 grams / day, at times 10 - 15 grams / day.In some examples, in which the conjugate or method comprise administration of D- cycloserine or any precursor thereof, D-cycloserine or any precursor thereof may be at a dosage of at a dosage of 100 mg- 1500 mg as a daily or bolus dosage administration, at times between250-1500 mg / day, at times between 200-500 mg / day, at times between 300-700 mg / day, at times between 350-1500 mg / day, at times between 400-800 mg / day, at times between 450-1500 mg / day, at times between 500-900 mg / day, at times between 550-1000 mg / day, at times between 700-1500 mg / day, at times between 1000-1500 mg / day, or any sub-range described herein.In some aspects, as used herein, the following Medical Dictionary for Regulatory Activities (MedDRA) terms are considered to be adverse events that are psychedelic in nature: altered mood, altered state of consciousness, autoscopy, delusional perception, disinhibition, dissociation, dissociative identity disorder, dreamy state, emotional disorder, euphoric mood, feeling abnormal, hallucination, hyperacusis, hyperaesthesia, hypoaesthesia, illusion, paranoia, parosmia, photophobia, sensory disturbance, time perception altered, thinking abnormal, synaesthesia, substance-induced psychotic distress, and somatic hallucination.In some embodiments, supplying the conjugates of this invention and an additional therapeutic agent, either as part of the composition or in separate compositions but administered simultaneously, or in a proximal time frame, as well constitute envisioned combination therapies of this invention, and further embodiments of this invention.According to this aspect and in some embodiments, the further therapeutic agent may be provided jointly, in a single or separate compositions, for concurrent treatment, in some aspects.As used herein, a therapy or therapeutic that is administered “concurrently” with another drug is administered, in some aspects, within 1 day of the other drug. In some embodiments, a therapy or therapeutic that is administered concurrently with another drug is administered at about the same time, within about 5 minutes, within about 10 minutes, within about 15 minutes, within about 20 minutes, within about 30 minutes, within about 45 minutes, within about 1 hour, within about 2 hours, within about 3 hours, within about 4 hours, within about 5 hours, within about 6 hours, within about 7 hours, within about 8 hours, within about 9 hours, within about 10 hours, within about 11 hours, within about 12 hours, within about 13 hours, within about 14 hours, within about 15 hours, within about 16 hours, within about 17 hours, within about 18 hours, within about 19 hours, within about 20 hours, within about 21 hours, within about 22 hours, within about 23 hours, or within about 24 hours of administration of the other drug.As noted herein, the conjugate may have a synergistic effect as compared to administration of each agent of which the conjugate is comprised is provided as a single therapy. A synergistic effect may be calculated, for example, using suitable methods such as, for example, the Sigmoid-Emax equation (Holford & Scheiner, 1981, Clin. Pharmacokinet. 6:429-453), the equation of Loewe additivity (Loewe & Muischnek, 1926, Arch. Exp. Pathol Pharmacol. 114:313-326) and the median-effect equation (Chou & Talalay, 1984, Adv. Enzyme Regul. 22:27-55).As described herein the conjugate may be considered as a slow-release system. Slow release (or sustained release) in the context of the conjugate refers a conjugate allowing gradual release of active compounds over a prolonged period, rather than an immediate or rapid release. This type of drug delivery system is used to maintain a steady therapeutic level of the drug in the bloodstream, minimize side effects, and potentially reduce the frequency of dosing.Hence, in accordance with some aspects, it is provided a slow-release conjugate as described herein.Slow release may be considered as a conjugate having a controlled or sustained release mechanism such that the active compounds in the conjugate are gradually delivered over an extended period of time. The release is characterized by a prolonged release profile in which the active substance is delivered at a slower rate compared to each one of the compounds separately, maintaining therapeutic levels over a desired duration.For sustained release, the compounds may be formulated with a suitable polymer or hydrophobic material which provides sustained release properties to the compounds. As such, the compounds for use with the method(s) described herein may be administered in the form of microparticles, for example, by injection or in the form of wafers or discs by implantation.In some cases, the dosage forms to be used can be provided as slow or controlled- release of one or more active ingredients therein using, for example, hydropropylmethyl cellulose, other polymer matrices, gels, permeable membranes, osmotic systems, multilayer coatings, microparticles, liposomes, or microspheres or a combination thereof to provide the desired release profile in varying proportions. Suitable controlled-release formulations known to those of ordinary skill in the art, including those described herein, can be readily selected for use with the pharmaceutical compositions described herein. Thus, single unit dosage forms suitable for oral administration, such as tablets, capsules, gelcaps, and caplets, that are adapted for controlled-release are encompassed by the compositions and dosage forms described herein.Most controlled-release pharmaceutical products have a common goal of improving drug therapy over that achieved by their non-controlled counterparts. Ideally, the use of an optimally designed controlled-release preparation in medical treatment is characterized by a minimum of drug substance being employed to cure or control the condition in a minimum amount of time.Advantages of controlled-release formulations include extended activity of the drug, reduced dosage frequency, and increased patient compliance. In addition, controlled-release formulations can be used to affect the time of onset of action or other characteristics, such as blood level of the drug, and thus can affect the occurrence of side effects.Most controlled-release formulations are designed to initially release an amount of drug that promptly produces the desired therapeutic effect, and gradually and continually release of other amounts of drug to maintain this level of therapeutic effect over an extended period of time. In order to maintain this constant level of drug in the body, the drug must be released from the dosage form at a rate that will replace the amount of drug being metabolized and excreted from the body. Controlled-release of an active ingredient can be stimulated by various inducers, for example pH, temperature, enzymes, water, or other physiological conditions or compounds. The term "controlled-release component" is defined herein as a compound or compounds, including, but not limited to, polymers, polymer matrices, gels, permeable membranes, liposomes, or microspheres or a combination thereof that facilitates the controlled-release of the active ingredient. In one embodiment, the compound(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation. In one embodiment, the compound(s) described herein are administered to a patient, alone or in combination with another pharmaceutical agent, using a sustained release formulation.The term delayed release is used herein in its conventional sense to refer to a drug formulation that provides for an initial release of the drug after some delay following drug administration and that may, although not necessarily, include a delay of from about 10 minutes up to about 12 hours. The term pulsatile release is used herein in its conventional sense to refer to a drug formulation that provides release of the drug in such a way as to produce pulsed plasma profiles of the drug after drug administration. The term immediate release is used in its conventional sense to refer to a drug formulation that provides for release of the drug immediately after drug administration.The term “alkyl” as used herein refers to a linear, branched saturated hydrocarbon having from 1 to 20 carbon atoms. The term “C1-C12 alkyl” or "C1-C12 alkylene” refers to a linear (straight), branched saturated hydrocarbon having from 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, in some embodiments, contain from 2 to 8 carbons, in yet some embodiments from 2 to 5 carbons, in yet some further embodiments, from 1 to 3 carbon atoms. It should benoted that alkyl refers to an alkyl end chain and alkylene refers to a middle chain alkyl. Representative C1-C12 alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, cyclopropyl, butyl, sec-butyl, iso-butyl, tert-butyl, cyclobutyl, pentyl, iso-pentyl, neopentyl, tert-pentyl, cyclopentyl, hexyl, cyclohexyl, heptyl, cycloheptyl, octyl, sec-octyl (1- methylheptyl), and cyclooctyl. The alkyl can be substituted or unsubstituted. When substituted, the substituent can be as described herein.The term “C1-C12 haloalkyl” as used herein refers to a C1-C12 alkyl as defined above, with one or more hydrogens substituted by halogen atoms.The term “alkenyl” as used herein refers to a linear (straight), branched unsaturated hydrocarbon having from 2 to 20 carbon atoms and at least one carbon-carbon double bond. The term “C2-C12 alkenyl” or "C2-C12 alkenylene" as used herein refers to a linear, branched unsaturated hydrocarbon having from 2 to 12 carbon atoms and at least one carbon-carbon double bond, in some embodiments from 3 to 8 carbons, in yet some further embodiments, from 3 to 5 carbon atoms and at least one double bond. It should be noted that alkenyl refers to an alkyl end chain and alkenylene refers to a middle chain alkyl.The term “C2-C12 haloalkenyl” as used herein refers to a C2-Ci2alkenyl as defined above, with one or more hydrogens substituted by halogen atoms.The term “alkynyl” as used herein refers to a linear, branched unsaturated hydrocarbon having from 2 to 20 carbon atoms and at least one carbon-carbon triple bond. The term “C2-C12 alkynyl” or "C2-C12 alkynylene" as used herein refers to a linear, branched unsaturated hydrocarbon having from 2 to 12 carbon atoms in certain embodiments, from 3 to 8 carbons, and at least one triple bond (at least one carbon-carbon triple bond). It should be noted that alkynyl refers to an alkyl end chain and alkynylene refers to a middle chain alkyl.The term “C2-C12 haloalkynyl” as used herein refers to a C2-C12 alkynyl as defined above, with one or more hydrogens substituted by halogen atoms.As used herein “alkoxy” refers to an alkyl group bonded to an oxygen atom. Similarly, the term “C1-C12 alkoxy!” as used herein refers to a C1-C12 alkyl group linked to an oxygen. At times, the alkyl group may include one to twelve carbon atoms, at times between one to eight carbon atoms, at times one to five carbon atoms and at times one to three carbon atoms. Representative examples are methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, sec-butoxy, tertbutoxy, pentoxy, isopentoxy, hexoxy, isohexoxy and the like. In certain embodiments, the alkoxy is ethoxy.The term “C1-C12 haloalkoxy” as used herein refers to a C1-C12 alkoxy as defined above, with one or more hydrogens substituted by halogen atoms.The term “halogen” (halo or halide) refers to F, Cl, Br or I.The term "cyano" describes a -ON group.The term "amino" as used herein encompass primary, secondary, tertiary or quaternary amines where the point of attachment is through the nitrogen atom which is substituted.The term "amide" describes a -C(=O)-NR'R" group, where R' and R" are any substituent as defined herein (for example any one of “R” substitutions).As used herein, “nitro” refers to -NO2.The term “hydroxy”, as used herein, refers to an -OH group.As used herein, “oxo” refers to =0.As used herein, “cycloalkyl” refers to a monocyclic or polycyclic radical that contains only carbon and hydrogen, and may be saturated, or partially unsaturated. Cycloalkyl groups include groups having from 3 to 12 ring atoms (i.e. C3-C10 cycloalkyl). Examples of cycloalkyl groups include, but are not limited to, groups such as cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, norbornyl, and the like.As used herein, “heterocycloalkyl” can be a stable 3- to 12-membered non-aromatic ring radical that comprises three to twelve carbon atoms and from one to six heteroatoms selected from nitrogen, oxygen and sulfur. Examples of heterocycloalkyl groups include, but are not limited to, groups such as dioxolanyl, thienyl[l,3]dithianyl, decahydroisoquinolyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidonyl, pyrrolidinyl, pyrrolidine, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuryl, tetrahydropyrrole, trithianyl, tetrahydropyranyl, thiomorpholinyl, thiamorpholinyl, 1-oxo-thiomorpholinyl, 1,1-dioxo-thiomorpholinyl, and the like.As used herein, “aryl” refers to a polyunsaturated, aromatic, hydrocarbon moiety which can be a single ring or multiple rings (e.g., 1 to 2 rings) which are fused together or linked covalently, having from six to twelve carbon atoms (i.e. C6-C12 aryl). Non-limiting examples of aryl groups include phenyl, 1 -naphthyl, 2-naphthyl, and 4-biphenyl.As used herein, the term “heteroaryl” refers to aryls as defined above where one or more carbons are substituted by heteroatoms. Exemplary heteroatoms include, but not limited to, nitrogen, sulfur, and oxygen. As used herein, " heteroaromatic" refers to refers to a monocyclic or multi-cyclic (fused) aromatic ring system, where one or more of the atoms in the ring system is a heteroatom, that is, an element other than carbon, including but not limited to, nitrogen, oxygen or sulfur. The term "heteroaromatic” used interchangeably with the term "heteroaryl" denotes a heterocyclic aromatic ring systems containing 5 to 12 atoms, with at least one, preferably two carbon atoms and one or more heteroatoms selected from nitrogen, oxygen and sulfur. Non-limiting examples include furan, thipohene, pyrrole, oxazole, oxadiazole, thiazole, imidazole, pyrazole, isoxazole, thiazolem benzofurna, indole, benzothiophene, benzoimidazole, indazole, benzoxazole, benzoisoxazole, benzothiazole, isobenzfuran, isoidole, purine, pyridine, pyrazine, pyrimidine, pyrisazine, quinoline, quinozaline, quinazoline, isoquinoline, furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, 1,2,3-triazolyl, 1,2,4- triazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,3-triazine, 1,2,4-triazine, 1,3,5-triazine, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5- thiadiazolyl, 1,3,4-thiadiazolyl, tetrazolyl, thiadiazinyl, [l,3,4]thiadiazole, thiadiazole, indolyl, isoindolyl, benzofuryl, benzothienyl, indazolyl, benzimidazolyl, benzothiazolyl, benzoisothiazolyl, benzoxazolyl, benzisoxazolyl, purinyl, quinazolinyl, quinolizinyl, quinolinyl, isoquinolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, azepinyl, diazepinyl, acridinyl and the like.Each one of the substitutions described herein may be optionally substituted by one or more substituents. The term “optionally substituted' refers to substitution with the named substituent or substituents, multiple degrees of substitution being allowed unless otherwise stated. The term substituted as used herein means that the compounds may contain one or more substituents, including, but not limited to, optionally substituted OH, CF3, halogen, C(=O), -COOH, -NH2, CN, alkyl, alkenyl, alkynyl, alkylene, straight alkenylene, alkynylene, haloalkyl, haloalkenyl, haloalkynyl, alkoxy, carboxyl, halogen, ring system including five to twelve atoms, aromatic or heteroaromatic ring, C(=O)- alkyl.It should be noted that the carbon number, as used herein, refers to the carbon backbone and carbon branching, but does not include carbon atoms of the substituents, such as alkoxy substitutions and the like.The term "pharmaceutically acceptable salt" refers to salts derived from organic and inorganic acids of a compound described herein. Exemplary salts include, but are not limited to, sulfate, citrate, acetate, oxalate, chloride, hydrochloride, bromide, hydrobromide, iodide, nitrate, bisulfate, phosphate, acid phosphate, isonicotinate, lactate, salicylate, acid citrate, tartrate, oleate, tannate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, camphorsulfonate, napthalenesulfonate, propionate, succinate, fumarate, maleate, malonate, mandelate, malate, phthalate, and pamoate. The term “pharmaceutically acceptable salt” as used herein also refers to a salt of a compound described herein having an acidic functional group, such as a carboxylic acid functional group, and a base. Exemplary bases include, but are not limited to, hydroxide of alkali metals including sodium, potassium, and lithium; hydroxides of alkaline earth metals such as calcium and magnesium; hydroxides of other metals, such as aluminum and zinc; ammonia, organic amines such as unsubstituted or hydroxyl-substituted mono-, di-, or tri-alkylamines, dicyclohexylamine; tributyl amine; pyridine; N-methyl, N-ethylamine; diethylamine; triethylamine; mono-, bis-, or tris-(2-OH-(Ci-C6)-alkylamine), such as N,N-dimethyl-N-(2-hydroxyethyl)amine or tri-(2-hydroxyethyl)amine; N-methyl-D-glucamine; morpholine; thiomorpholine; piperidine; pyrrolidine; and amino acids such as arginine, lysine, and the like. The term “pharmaceutically acceptable salt” also includes hydrates of a salt of a compound described herein.The term “solvate” refers to an aggregate of a molecule with one or more solvent molecules, such as hydrate, alcoholate (aggregate or adduct with alcohol), and the like.The term “hydrate” refers to a compound formed by the addition of water. The hydrates may be obtained by any known method in the art by dissolving the compounds in water and recrystallizing them to incorporate water into the crystalline structure.The term "stereoisomer” as used herein is meant to encompass an isomer that possess identical constitution as a corresponding stereoisomer, but which differs in the arrangement of its atoms in space from the corresponding stereoisomer.In accordance with some embodiments, the conjugates of this invention include mixtures of enantiomers (possibly as a racemic mixture) as well as purified enantiomers or enantiomerically enriched mixtures. The present invention also encompasses the individual enantiomer(s) (i.e. R or S or D or L, preferably D) of the conjugates being represented by the formulas above as racemic mixtures. Methods of preparing substantially isomerically purecompounds are known in the art. If, for instance, a particular enantiomer of a conjugate of the present disclosure is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts may be formed with an appropriate optically active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers. Alternatively, enantiomerically enriched mixtures and pure enantiomeric compounds can be prepared by using synthetic intermediates that are enantiomerically pure in combination with reactions that either leave the stereochemistry at a chiral center unchanged or result in its complete inversion. Techniques for inverting or leaving unchanged a particular stereocenter, and those for resolving mixtures of stereoisomers are well known in the art, and it is well within the ability of one of skill in the art to choose an appropriate method for a particular situation.It should be noted that certain of the compounds (of the conjugate) described herein may contain one or more chiral atoms. The present invention also covers the individual enantiomers of the conjugates represented by the formulas above. In some embodiments, a conjugate of the invention comprises a chirally pure enantiomer. In some embodiments, the compound of the invention comprises at least 99% chirally pure enantiomer. In some examples, the conjugate comprises one or more compounds in a chiral arrangement being D configuration. The terms “enantiomerically pure”, “enantiomeric purity”, “chiral purity” and “chirally pure” reflect the fact that one enantiomer is found in the composition in greater proportion in relation to its mirror image. The proportion between two enantiomers is expressed by the absolute proportion of one of the enantiomers, which is at least 70%, at least 80%, at least 90%, at least 95%, at least 98%, and at least 99% or more.As used herein the term isotopologue refers to a compound that differs from a specific compound only in the isotopic composition of one or more of their atoms thereof. In other words, an isotopologue of a compound have the same molecular structure, including the same sequence of bonded atoms, but differ in the isotopes of one or more of these atoms. For example, one or more of hydrogen atoms in a compound may be2H (deuterium).As noted above, the invention provides methods for treating diseases or disorders specified above.As used herein, “disease”, “disorder”, “condition” and the like, as they relate to a subject's health, are used interchangeably and have meanings ascribed to each and all of such terms. It is understood that the interchangeably used terms "associated" and "related", when referring to pathologies herein, mean diseases, disorders, conditions, or any pathologies which at least one of: share causalities, co-exist at a higher than coincidental frequency, or where at least one disease, disorder, condition or pathology causes a second disease, disorder, condition or pathology.According to this aspect and in some embodiments, “treatment-resistant” conditions refer to a failure to respond to known treatments when provided at sufficient dosage for a sufficient time to typically elicit a therapeutic effect in other subjects with the same condition.The term “treatment” as used herein refers to the administering of a therapeutic amount of the conjugate or composition of the present invention which is effective to improve one or more undesired symptoms associated with a disease or condition as described herein. Further, the terms "treat”, “treating”, “treatment" or forms thereof, as used herein, mean preventing, ameliorating or delaying the onset of one or more clinical indications of disease activity in a subject having a pathologic disorder. Treatment refers to therapeutic treatment. Those in need of treatment are subjects suffering from a pathologic disorder. Specifically, providing a "preventive treatment" (to prevent) or a "prophylactic treatment" is acting in a protective manner, to defend against or prevent something, especially a condition or disease. The term “treatment or prevention” as used herein, refers to the complete range of therapeutically positive effects of administrating to a subject including inhibition, reduction of, alleviation of, and relief from, a condition as described herein.The present invention relates to the treatment of subjects or patients, in need thereof. By “patient” or “subject in need” it is meant any organism who may be affected by the above- mentioned conditions, and to whom the therapeutic and prophylactic methods herein described are desired, including humans, domestic and non-domestic mammals such as canine and feline subjects, bovine, simian, equine and rodents, specifically, murine subjects. More specifically, the methods of the invention are intended for mammals. By “mammalian subject” is meant any mammal for which the proposed therapy is desired, including human, livestock, equine, canine, and feline subjects, most specifically humans.The term "effective amount” relates to the amount of the conjugate present in a composition, that is needed to provide a desired level of active agent in the bloodstream or at the site of action in an individual to be treated to give an anticipated physiological responsewhen such composition is administered. The precise amount will depend upon numerous factors, e.g., the active agent, the activity of the composition, the delivery device employed, the physical characteristics of the composition, intended patient use (i.e., the number of doses administered per day), patient considerations, and the like, and can readily be determined by one skilled in the art, based upon the information provided herein. It should be noted that the composition / s of the invention and any components thereof may be applied as a single daily dose or multiple daily doses, or every other day, once a week, once in 10 days, once in 2 weeks, etc.Administration of the conjugates / combinations / compositions described herein to a patient, preferably a mammal, more preferably a human, may be carried out using known procedures, at dosages and for periods of time effective to treat a neurological disease or disorder or treat a disease or disorder that is affected by, associated with, or would benefit from the combination therapies described herein, in the patient. An effective amount of the therapeutic compound necessary to achieve a therapeutic effect may vary according to factors such as the state of the disease or disorder in the patient; the age, sex, and weight of the patient; and the ability of the therapeutic compound to treat a neurological disease or disorder or treat a disease or disorder that is affected by, associated with, or would benefit from the combination therapies as herein described, in the patient.Dosage regimens may be adjusted to provide the optimum therapeutic response. For example, several divided doses may be administered daily or the dose may be proportionally reduced as indicated by the exigencies of the therapeutic situation. One of ordinary skill in the art would be able to study the relevant factors and make the determination regarding the effective amount of the therapeutic compound without undue experimentation.Actual dosage levels of the active ingredients in the pharmaceutical compositions described herein may be varied so as to obtain an amount of the active ingredient that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, without being toxic to the patient. In particular, the selected dosage level depends upon a variety of factors including the activity of the particular compound employed, the time of administration, the rate of excretion of the compound, the duration of the treatment, other drugs, compounds or materials used in combination with the compound, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well, known in the medical arts.In particular embodiments, it is especially advantageous to formulate the conjugates / combinations / compositions in dosage unit form for ease of administration and uniformity of dosage. Dosage unit form as used herein refers to physically discrete units suited as unitary dosages for the patients to be treated; each unit containing a predetermined quantity of therapeutic compound calculated to produce the desired therapeutic effect in association with the required pharmaceutical vehicle. The dosage unit forms of the compound(s) described herein are dictated by and directly dependent on (a) the unique characteristics of the therapeutic compound and the particular therapeutic effect to be achieved, and (b) the limitations inherent in the art of compounding / formulating such a therapeutic compound.In certain embodiments, the compositions described herein are formulated using one or more pharmaceutically acceptable excipients or carriers. In certain embodiments, the pharmaceutical compositions described herein comprise a therapeutically effective amount of a compound described herein and a pharmaceutically acceptable carrier.The carrier may be a solvent or dispersion medium containing, for example, water, ethanol, polyol (for example, glycerol, propylene glycol, and liquid polyethylene glycol, and the like), suitable mixtures thereof, and vegetable oils. The proper fluidity may be maintained, for example, by the use of a coating such as lecithin, by the maintenance of the required particle size in the case of dispersion and by the use of surfactants.In other embodiments, the compositions are specifically formulated to promote delayed absorption of active ingredients as described herein in oral formulations, or in some embodiments, in dermally applied formulations, such as skin patches and the like. The skilled artisan will readily recognize the means to accomplish same, which include standard pharmaceutical preparations known in the art.In certain embodiments, the compositions described herein are administered to the patient in dosages that range from one to five times per day or more. In other embodiments, the compositions described herein are administered to the patient in range of dosages that include, but are not limited to, once every day, every two days, every three days to once a week, and once every two weeks. It is readily apparent to one skilled in the art that the frequency of administration of the various combination compositions described herein varies from individual to individual depending on many factors including, but not limited to, age, disease or disorder to be treated, gender, overall health, and other factors. Thus, administration of the compounds and compositions described herein should not be construed to be limited to any particular dosageregime and the precise dosage and composition to be administered to any patient is determined by the attending physician taking all other factors about the patient into account.In certain embodiments, a composition as described herein is a packaged pharmaceutical composition comprising a container holding a therapeutically effective amount of a compound described herein, alone or in combination with a second pharmaceutical agent; and instructions for using the compound to treat, prevent, or reduce one or more symptoms in a patient of a disease or disorder as described herein.Formulations may be employed in admixtures with conventional excipients, pharmaceutically acceptable organic or inorganic carrier substances suitable for oral, parenteral, nasal, intravenous, subcutaneous, enteral, or any other suitable mode of administration, known to the art. The pharmaceutical preparations may be sterilized and if desired mixed with auxiliary agents, e.g., lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure buffers, coloring, flavoring and / or aromatic substances and the like.Routes of administration of any one of the compositions described herein include oral, nasal, rectal, intravaginal, parenteral, buccal, sublingual or topical. The compounds for use in the compositions described herein can be formulated for administration by any suitable route, such as for oral or parenteral, for example, transdermal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), (intra)nasal and (trans)rectal), intravesical, intrapulmonary, intraduodenal, intragastrical, intrathecal, subcutaneous, intramuscular, intradermal, intra-arterial, intravenous, intrabronchial, inhalation, and topical administration.Suitable compositions and dosage forms include, for example, tablets, capsules, caplets, pills, gel caps, troches, dispersions, suspensions, solutions, syrups, granules, beads, sachets, transdermal patches, gels, powders, pellets, magmas, lozenges, creams, pastes, plasters, lotions, discs, suppositories, liquid sprays for nasal or oral administration, dry powder or aerosolized formulations for inhalation, compositions and formulations for intravesical administration and the like.For oral application or administration, particularly suitable are tablets, dragees, liquids, drops, suppositories, or capsules, caplets and gelcaps. The compositions intended for oral use may be prepared according to any method known in the art and such compositions may contain one or more agents selected from the group consisting of inert, non-toxic pharmaceuticallyexcipients that are suitable for the manufacture of tablets. Pharmaceutically acceptable excipients such as binding agents, fillers, lubricants, or wetting agents. Excipients may also include, for example an inert diluent such as lactose; granulating and disintegrating agents such as cornstarch; binding agents such as starch; and lubricating agents such as magnesium stearate. The tablets may be uncoated or they may be coated by known techniques for elegance or to delay the release of the active ingredients. Formulations for oral use may also be presented as hard gelatin capsules wherein the active ingredient is mixed with an inert diluent.. Liquid preparation for oral administration may be in the form of solutions, syrups or suspensions.Compositions as described herein can be prepared, packaged, or sold in a formulation suitable for oral or buccal administration. A tablet that includes a compound as described herein can, for example, be made by compressing or molding the active ingredient, optionally with one or more additional ingredients. Pharmaceutically acceptable excipients used in the manufacture of tablets include, but are not limited to, inert diluents, granulating and disintegrating agents, dispersing agents, surface-active agents, disintegrating agents, binding agents, and lubricating agents.Suitable dispersing agents include, but are not limited to, potato starch, sodium starch gly collate, poloxamer 407, or poloxamer 188.Surface-active agents (surfactants) include cationic, anionic, or non-ionic surfactants, or combinations thereof.Suitable diluents include, but are not limited to, calcium carbonate, magnesium carbonate, magnesium oxide, sodium carbonate, lactose, microcrystalline cellulose, calcium phosphate, calcium hydrogen phosphate, and sodium phosphate, Cellactose ® 80 (75 % a- lactose monohydrate and 25 % cellulose powder), mannitol, pre-gelatinized starch, starch, sucrose, sodium chloride, talc, anhydrous lactose, and granulated lactose.Suitable granulating and disintegrating agents include, but are not limited to, sucrose, copovidone, com starch, microcrystalline cellulose, methyl cellulose, sodium starch glycollate, pregelatinized starch, povidone, sodium carboxy methyl cellulose, sodium alginate, citric acid, croscarmellose sodium, cellulose, carboxymethylcellulose calcium, colloidal silicone dioxide, crosspovidone and alginic acid.Suitable binding agents include, but are not limited to, gelatin, acacia, pre-gelatinized maize starch, polyvinylpyrrolidone, anhydrous lactose, lactose monohydrate, hydroxypropyl methylcellulose, methylcellulose, povidone, polyacrylamides, sucrose, dextrose, maltose, gelatin, polyethylene glycol.Suitable lubricating agents include, but are not limited to, magnesium stearate, calcium stearate, hydrogenated castor oil, glyceryl monostearate, glyceryl behenate, mineral oil, polyethylene glycol, pol oxamer 407, pol oxamer 188, sodium laureth sulfate, sodium benzoate, stearic acid, sodium stearyl fumarate, silica, and talc.Tablets can be non-coated or they may be coated using known methods to achieve delayed disintegration in the gastrointestinal tract of a subject, thereby providing sustained release and absorption of the active ingredient. Further by way of example, tablets may be coated using methods described in U.S. Patent Nos. 4,256,108; 4,160,452; and 4,265,874.Tablets can also be enterically coated such that the coating begins to dissolve at a certain pH, such as at about pH 5.0 to about pH 7.5, thereby releasing a compound as described herein.For parenteral administration, the compounds as described herein may be formulated for injection or infusion, for example, intravenous, intramuscular or subcutaneous injection or infusion, or for administration in a bolus dose and / or continuous infusion. Suspensions, solutions or emulsions in an oily or aqueous vehicle, optionally containing other formulatory agents such as suspending, stabilizing and / or dispersing agents may be used.Sterile injectable forms of the compositions described herein may be aqueous or oleaginous suspension. These suspensions may be formulated according to techniques known in the art using suitable dispersing or wetting agents and suspending agents.Additional dosage forms suitable for use with the compound(s) and compositions described herein include dosage forms as described in U.S. Patents Nos. 6,340,475; 6,488,962; 6,451,808; 5,972,389; 5,582,837; and 5,007,790; and U.S. Patent Applications Nos. 20030147952; 20030104062; 20030104053; 20030044466; 20030039688; and 20020051820.In certain embodiments, the formulations described herein can be, but are not limited to, short-term, rapid-offset, as well as controlled, for example, sustained release, delayed release and pulsatile release formulations. The term sustained release is used in its conventional sense to refer to a drug formulation that provides for gradual release of a drug over an extended period of time, and that may, although not necessarily, result in substantially constant blood levels of adrug over an extended time period. The period of time may be as long as a month or more and should be a release which is longer that the same amount of agent administered in bolus form.The term "about" as used herein indicates values that may deviate up to 1%, more specifically 5%, more specifically 10%, more specifically 15%, and in some cases up to 20% higher or lower than the value referred to, the deviation range including integer values, and, if applicable, non-integer values as well, constituting a continuous range. In some embodiments, the term "about" refers to ± 10 %.The indefinite articles “a” and “an,” as used herein in the specification and in the claims, unless clearly indicated to the contrary, should be understood to mean “at least one.” It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise.As used herein in the specification and in the claims, the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified.It should also be understood that, unless clearly indicated to the contrary, in any methods claimed herein that include more than one step or act, the order of the steps or acts of the method is not necessarily limited to the order in which the steps or acts of the method are recited.It should be noted that various embodiments of this invention may be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the invention. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range. Whenever a numerical range is indicated herein, it is meant to include any cited numeral (fractional or integral) within the indicated range. Thephrases "ranging / ranges between" a first indicate number and a second indicate number and "ranging / ranges from" a first indicate number "to" a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numerals there between.It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable sub combination or as suitable in any other described embodiment of the invention. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.The following examples are representative of techniques employed by the inventors in carrying out aspects of the present invention. It should be appreciated that while these techniques are exemplary of preferred embodiments for the practice of the invention, those of skill in the art, in light of the present disclosure, will recognize that numerous modifications can be made without departing from the spirit and intended scope of the invention.NON-LIMITING EXAMPLESEXAMPLE 1: Synthesis of conjugates of psychedelics and NMD AR modulators:A general chemical synthetic scheme for the preparation of a compound of Formula 1, 1-1 and I- 2 may be as follows:wherein Rl, R2 are as herein defined.For example, and representing an embodied aspect of the invention, a general chemical synthetic scheme for the preparation of the compound of Formula 1-2’ may be described by the followingscheme:In a first step, afford (2-[4-(benzyloxy)-2,3-dihydro-lH-indol-3-yl]ethyldiisopropylamine is prepared from (2-[4-(benzyloxy)-lH-indol-3-yl]ethyldiisopropylamine, as follows:To a solution of (2-[4-(benzyloxy)-lH-indol-3-yl]ethyldiisopropylamine (4.7 g, 13.4 mmol) in trifluoroacetic acid (50 mL) was added triethylsilane (4.68 g, 40.2 mmol) , the resulting solution was stirred for 10 hours at room temperature. The resulting mixture was concentrated under vacuum. The residue was dissolved in DMF and adjusted to PH = 8 with DIEA. The resulting mixture was purified by a reversed-phase flash chromatography directly with the following conditions: column, C18 silica gel; mobile phase, A: water, B: ACN, B% (5%~ 80% in 40 min); Detector, UV 210 nm to afford (2-[4-(benzyloxy)-2,3-dihydro-lH-indol-3- yl] ethyldiisopropylamine (2.9 g, 42.94% yield) as a brown oil. LC-MS: (ESI, m / z) 353.40[M+l]+In a next step, 4-[4-(benzyloxy)-3-[2-(diisopropylamino)ethyl]-2,3-dihydroindole-l-carbonyl]- l,3-oxazolidin-2-one is prepared from the obtained product above, (2-[4-(benzyloxy)-2,3- dihydro-lH-indol-3-yl]ethyldiisopropylamineA solution of (2-[4-(benzyloxy)-2,3-dihydro-lH-indol-3-yl]ethyldiisopropylamine (1.55 g, 4.4 mmol), 2-oxo- l,3-oxazolidine-4-carboxylic acid (0.58 g, 4.4 mmol), TBTU (2.12 g, 6.6 mmol) and DIEA (1.70 g, 13.2 mmol) in N,N-dimethylformamide (30 mL) was stirred for 1.5 hours at room temperature. The reaction system was purified by a reversed-phase flash chromatography directly with the following conditions: column, C18 silica gel; mobile phase, A: water, B: ACN, B% (5%~ 50% in 30 min); Detector, UV 210 nm to afford 4-[4-(benzyloxy)-3-[2- (diisopropylamino)ethyl]-2,3-dihydroindole-l-carbonyl]-l,3-oxazolidin-2-one (1.2 g, 41.03% yield) as a brown soild. LC-MS: (ESI, m / z) 466.25[M+1]+In the final step, the compound of Formula 1-2’ is prepared from the 4-[4-(benzyloxy)-3-[2- (diisopropylamino)ethyl]-2,3-dihydroindole-l-carbonyl]-l,3-oxazolidin-2-one product obtained in the previous step, as follows:Under hydrogen (2 atm), a mixture of 4-[4-(benzyloxy)-3-[2-(diisopropylamino)ethyl]-2,3- dihydroindole-1 -carbonyl] -l,3-oxazolidin-2-one (800 mg, 1.7 mmol) and Pd / C (400 mg, 3.8 mmol) in methanol (30 mL) was stirred at room temperature for 1 hour. The resulting mixture was filtered, the filter cake was washed with methanol (6 x 20 mL). The filtrate was concentrated under reduced pressure. The residue was purified by Prep-HPLC directly with the following conditions (Column, XSelect CSH C18 Column 19*150mm 5um; mobile phase, A: 0.1% FA in water, B: ACN and B% (2%~15% in 10 min); Detector, UV 210 nm) to afford 4-(3-[2-(diisopropylamino)ethyl]-4-hydroxy-2,3-dihydroindole-l-carbonyl-l,3-oxazolidin-2-one (105 mg, 16.2% yield) as a white solid.NMR (400 MHz, DMSO-6, ppm) 5 8.28 (s, 1H), 8.18 - 8.05 (m, 1H), 7.65 - 7.52 (m, 1H), 7.05 - 6.95 (m, 1H), 6.55 - 6.45 (m, 1H), 4.90 - 4.75 (m, 1H), 4.70 - 4.50 (m, 2H), 4.25 - 4.15 (m, 1H), 4.05 - 3.90 (m, 1H), 3.80 - 3.70 (m, 1H), 3.21 - 3.01 (m, 2H), 2.70 - 2.55 (m, 2H), 2.15 - 1.95 (m, 1H), 1.60 - 1.40 (m, 1H), 1.15 -.0.95 (m, 12H). LC-MS: (ESI, m / z) 376.20[M+l]+In addition to the preparation of the Compound of Formula 1-2’, the Compound of Formula II-2 was also prepared.A general chemical synthetic scheme for the preparation of a compound of Formula II, II- 1 and II-2 is as provided in the following scheme, wherein R1 and R2 are as herein defined:With the general synthetic scheme for a compound of formula II-2 provided as follows:In a first step, 2-[4-(benzyloxy)-lH-indol-3-yl]-N,N-diisopropyl-2-oxoacetamide is prepared from 4-(benzyloxy)-lH-indole, as follows:To a solution of 4-(benzyloxy)-lH-indole (20 g, 89.6 mmol) in diethyl ether (300 mL) was added oxalyl chloride (34.11 g, 268.7 mmol) by dropwise at 0 °C. The resulting solution was stirred for 2 hours at room temperature. The reaction system was added to the solution of diisopropylamine (36.26 g, 358.3 mmol) in diethyl ether (500 mL) by dropwise at -78 °C and stirred at -78 °C for 0.5 hours. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with DCM / EA (45 / 55) to afford 2-[4-(benzyloxy)-lH-indol-3- yl]-N,N-diisopropyl-2-oxoacetamide (15.6 g, 42.79% yield) as a brown soild. LC-MS: (ESI, m / z 379.00[M+l]+-

[0001] In a next step, (2-[4-(benzyloxy)-lH-indol-3-yl]ethyldiisopropylamine is prepared from 2-[4-(benzyloxy)-lH-indol-3-yl]-N,N-diisopropyl-2-oxoacetamide, as follows:To a solution of 2-[4-(benzyloxy)-lH-indol-3-yl]-N,N-diisopropyl-2-oxoacetamide (15.6 g, 41.2 mmol) in tetrahydrofuran (600 mL) was added Li Al PL (9.23 g, 243.2 mmol) bybatches at 0 °C. The resulting mixture was stirred for 10 hours at 65 °C. The reaction was quenched with 20 mL Water, 20 mL 15% NaOH (aq.) and 80 mL Water at 0 °C. The resulting mixture was filtered, the filter cake was washed with ethyl acetate (6 x 200 ml). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with DCM / EA (30 / 70) to afford (2-[4-(benzyloxy)- lH-indol-3-yl]ethyldiisopropylamine (11 g, 70.12% yield) as a brown oil. LC-MS: (ESI, m / z): 351.10[M+l]+.In a next step, tert-butyl 4-(benzyloxy)-3-[2-(diisopropylamino)ethyl]indole-l- carboxylate is prepared from 2-[4-(benzyloxy)-lH-indol-3-yl]ethyldiisopropylamine, as follows:To a solution of (2-[4-(benzyloxy)-lH-indol-3-yl]ethyldiisopropylamine (5 g, 14.3 mmol) in dichloromethane (100 mL) were added DMAP (175 mg, 1.43 mmol), DIEA (3.69 g, 28.5 mmol) and BOC2O (4.67 g, 21.5 mmol), the resulting solution was stirred for 1 hour at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (45 / 55) to afford tert-butyl 4-(benzyloxy)-3-[2-(diisopropylamino)ethyl]indole-l- carboxylate (3.8 g, 58.46% yield) as a brown yellow oil. LC-MS: (ESI, m / z) 451.10[M+l]+.In a further step, tert-butyl 3-[2-(diisopropylamino)ethyl]-4-hydroxyindole-l-carboxylate is prepared from tert-butyl 4-(benzyloxy)-3-[2-(diisopropylamino) ethyl] indole- 1- carboxylate, as follows:Under hydrogen (2 atm), a mixture of tert-butyl 4-(benzyloxy)-3-[2-(diisopropylamino) ethyl] indole- 1 -carboxylate (3.8 g, 8.4 mmol) and Pd / C (895 mg, 8.4 mmol) in ethyl acetate (50 mL) was stirred at room temperature for 10 minutes. The resulting mixture was filtered, the filter cake was washed with ethyl acetate (6 x 20 mL). The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with PE / EA (40 / 60) to afford tert-butyl 3-[2- (diisopropylamino)ethyl]-4-hydroxyindole-l -carboxylate (2 g, 62.37% yield) as a brown yellow oil. LC-MS: (ESI, m / z) 361.00[M+l]+.In a next step, tert-butyl 3-[2-(diisopropylamino)ethyl]-4-(([(4R)-3-oxo-l,2-oxazolidin- 4-yl]carbamoyloxy)indole-l -carboxylate is prepared from tert-butyl 3-[2- (diisopropylamino)ethyl] -4-hydroxyindole- 1 -carboxylate, as follows :To a solution of tert-butyl 3-[2-(diisopropylamino)ethyl]-4-hydroxyindole-l-carboxylate (2 g, 5.6 mmol,) in tetrahydrofuran (80 mL) was added NaH (106.5 mg, 4.4 mmol) slowly at 0 °C. The resulting mixture was stirred for 1 hour at room temperature. The reaction system was added to the solution of 4-nitrophenyl carbonochloridate (5.59 g, 27.7 mmol) in tetrahydrofuran (80 mL) at 0 °C. The resulting mixture was stirred for 1 hour at room temperature. Then a solution of cycloserine (2.83 g, 27.7 mmol) in dimethylsulfoxide (80 mL) was added to the reaction system slowly at 0 °C. The resulting mixture was stirred for 0.5 hours at room temperature. The resulting mixture was purified by a reversed-phase flash chromatography directly with the following conditions: column, C18 silica gel; mobile phase, A: 0.5% HC1 in water, B: ACN, B% (2%~ 32% in 60 min); Detector, UV 254 nm to afford tert-butyl 3-[2-(diisopropylamino)ethyl]-4-(([(4R)-3-oxo- l,2-oxazolidin-4-yl]carbamoyloxy)indole-l -carboxylate (450 mg, 13.23% yield) as a yellow soild. LC-MS: (ESI, m / z): 489.15[M+1]+.In a final step, 3-[2-(diisopropylamino)ethyl]-lH-indol-4-yl N-[(4R)-3-oxo-l,2- oxazolidin-4-yl]carbamate hydrochloride is prepared from tert-butyl 3-[2- (diisopropylamino)ethyl]-4-(([(4R)-3-oxo-l,2-oxazolidin-4-yl]carbamoyloxy)indole-l- carboxylate, as follows:A solution of tert-butyl 3-[2-(diisopropylamino)ethyl]-4-(([(4R)-3-oxo-l,2-oxazolidin-4- yl]carbamoyloxy)indole-l-carboxylate (450 mg, 0.9 mmol) in 0.5% HC1 (aq.) (20 mL) was stirred for 96 hours at room temperature. The resulting mixture was concentrated under reduced pressure. The residue was purified by a reversed-phase flash chromatography with the following conditions: column, C18 silica gel; mobile phase, A: 0.5% HC1 in water, B: ACN, B% (2% to 17% in 30 min); detector, UV 220 nm to afford 3-[2-(diisopropylamino)ethyl]-lH-indol-4-yl N-[(4R)-3-oxo-l,2-oxazolidin-4- yl]carbamate hydrochloride (101.1 mg, 27.13% yield) as a grey soild.

[0002] 11.95 - 11.51 (m, 1H), 11.20 (s, 1H), 9.68 - 9.10 (m, 1H), 8.65 - 8.42 (m, 1H), 7.36 (s, 1H), 7.30 - 7.19 (m, 1H), 7.15 - 7.05 (m, 1H), 6.90 - 6.68 (m, 1H), 4.85 - 4.40 (m, 2H), 4.25 - 4.08 (m, 1H), 3.85 - 3.60 (m, 3H), 3.25 - 3.10 (m, 3H), 1.50 -.1.15 (m, 12H). LC-MS: (ESI, m / z) 389.20[M+l]+.Thus, non-limiting embodied conjugates of the invention have been synthesized and characterized as described herein.EXAMPLE 2: The effect of conjugate on psychedelic tripMaterial and methodsHead twitch response (HTR) was measured over 30 minutes by means of a magnetometer apparatus. Small neodymium magnets (N50, 3mm diameter x 1mm height, 50 mg), were attached to the outer ears of mice. After a 5-7-day recovery period, the ear- tagged animals were placed inside a magnetometer apparatus immediately after injection of vehicle, or drug. The output was amplified (Pyle PP444 phono amplifier) and recorded at 1000 Hz using a NI USB6001 (National Instruments, US) data acquisition system. Recordings were performed using a MATLAB driver (MathWorks, US, R2021a version, along with the NI myDAQ support package) with the corresponding National Instruments support package for further processing. A custom MATLAB script was used to record the processed signal, which was presented as graphs showing the change in current as peaks (mAh). A custom graphic user interface created in our laboratory was used to further process the recording into an Excel spreadsheet.ResultsInitially, the head twitch response (HTR) for 4-OH-DiPT at three doses (2mg / kg, 4mg / kg, 6mg / kg) was tested.As can be seen in Figure 1 and Figure 2, all three doses elicited a strong HTR with a similar total HTR over 30 minutes but slightly different time courses.The HTR was then assessed for HBL20018.Two dosages of HBL20018 were selected for testing 7.85mg / kg and 50mg / kg. The dose of 7.85mg / kg was selected as it is equimolar to 6.0mg / kg of 4-OH-DiPT and the dose of 50mg / kg was selected as it is equimolar to 38mg / kg of 4-OH-DiPT. The higher amount was selected in attempt to maximize the amount of D-cycloserine delivered via the metabolic cleavage of the conjugate.Table 1 shows the selected doses.As can be seen in Figure 3 and Figure 4, 4-OH-DiPT 6 mg / kg induced significant HTR which lasted for 30 minutes while 38 mg / kg 4-OH-DiPT induced an initial peak that was less than half of that induced by 6 mg / kg and dissipated to 0 by 6 minutes. The lack of effect of the higher dose is most likely a reflection of toxicity.As can be further seen in Figure 3 and Figure 4, the time course of HTR induced by HBL20018 7.85 mg / kg is distinctly different from that of 4-OH-DiPT 6 mg / kg and that of other previously tested psychedelic tryptamines (data not shown). Specifically, the onset of the HTR induced by HBL20018 was delayed and increased minimally over the course of the 30- minute recording window. HBL20018 50 mg / kg induced more HTR than HBL20018 6 mg / kg, most likely due to the higher concentration of 4-OH-DIPT in the conjugate.It is suggested that the mechanism that accounts for the difference in HTR between HBL20018 and 4-OH-DiPT may be due to time required for the cleavage of the conjugate acting as a slow-release system of the two conjugated drugs.EXAMPLE 3: D-SER or DCS Reduce or Abrogate Psychedelic Trip Effects Induced by PsilocybinThe head twitch response (HTR) induced by serotonergic psychedelic agents such as psilocybin (PSIL) in rodents, is a characteristic behavioral effect mediated by cortical 5-HT2A receptors that is highly correlated with the psychedelic trip induced by these agents in humans.HTR induced by PSIL in C57Bl / 6j mice has been extensively characterized.In order to determine whether the negative effects such as HTR could be blocked in schizophrenic patients administered psilocybin (PSIL) -containing conjugates (which ordinarily would produce “trip-induced effects”) upon further receiving D-Serine (D- SER) or D-cycloserine (DCS), the effect of conjugate treatment in the manifestation of the HTR-inducing effect of PSIL in mice is examined.Toward this end, male ICR mice (aged 8 weeks) are implanted with mini ear-magnets and administered the conjugates intraperitoneally (i.p.):1. PSIL2. Vehicle (Saline) controls3. Conjugates.HTR is assessed over a 20-minute period using a purpose-built magnetometer and custom software.Total HTR in each of the treatment groups over a 20-minute period will be assessed (mean + standard error). PSIL alone will induce a significant increase in total HTR over the observation period in comparison to vehicle controls. Conjugate treated mice isexpected to show a significantly reduced HTR, in comparison to PSIL alone treated animals, approaching control levels.EXAMPLE 4: Effect of Conjugates on hyperactivity induced by the NMDA receptor antagonist, MK-801Hyperactivity induced in rodents by the NMD AR antagonist, MK-801, is a key rodent pharmacological model of acute psychotic features in humans.Drugs which induce psychosis in humans enhance MK-801 induced hyperactivity in rodents while antipsychotic drugs reduce or block the effect.ICR mice are administered MK-801 intra-peritoneally, at a dose of 0.1 mg / kg immediately before they were placed in an open field for one hour. 30 minutes prior to administration of MK-801, mice are pretreated with the conjugates at various dosages, and compared to individual treatment and saline controls, as well.Activity in the open field is monitored by an overhead camera and recorded by a Noldus Ethovision apparatus. Distance moved / travelled in the open field, center duration and center frequency are evaluated in the open field arena.MK-801 treatment produces marked movement, reflecting MK-801 induced hyperactivity. PSIL treatment alone does not enhance MK-801 induced hyperactivity.In the acute MK-801-induced hyperlocomotion test, whether there is a significant difference in the distance travelled between mice administered saline prior to MK-801 injection and mice administered the conjugates will be evaluated.EXAMPLE 5: Effect of Conjugate treatment in Promoting NeuroplasticitvICR mice are administered the conjugates and compared to animals given a single intraperitoneal injection of psilocybin at a dosage of 4.4 mg / kg, and control animals (administered a saline vehicle). 7 days post-administration, animals are harvested, and individual brain regions are dissected, homogenized and processed for Western Blotanalysis, probing for GAP43, Synaptophysin and SV2A protein expression, using commercially available reagents (Abeam).Animals injected with conjugates and each component are specifically probed for changes in synaptic protein expression, for proteins that are pivotally involved in neuroplasticity of the brain, focusing on 4 key regions: the brain frontal cortex, hippocampus, amygdala and striatum.The synaptic proteins, GAP43, PSD95, Synaptophysin and SV2A are assessed in terms of expression levels, in the frontal cortex and amygdala of treated subjects as are the hippocampus and striatum.

Claims

CLAIMS:

1. A conjugate comprising at least one psychedelic compound or a precursor thereof and at least one N-methyl D-aspartate (NMDA) receptor (NMDAR) modulator or a precursor thereof.

2. The conjugate according to claim 1, wherein said at least one psychedelic compound or a precursor thereof being covalently associated with said at least one NMDAR modulator or a precursor thereof.

3. The conjugate according to claim 1, wherein said psychedelic compound or a precursor thereof is a serotonergic psychedelic compound or a precursor thereof.

4. The conjugate according to claim 1 or 2, wherein said psychedelic compound or a precursor thereof is a 5-HT2A receptor agonist.

5. The conjugate according to any one of claims 1 to 3, wherein the psychedelic compound or a precursor thereof is one or more of a tryptamine compound or precursor thereof, a phenethylamine compound or precursor thereof, a lysergamide compound or precursor thereof, an ergoline compound or precursor thereof, or any combination thereof.

6. The conjugate according to any one of claims 1 to 5, wherein the psychedelic compound or a precursor thereof is a tryptamine compound or precursor thereof selected from the group consisting of psilocybin (4-phosphoryloxy- / V, / V-di methyl tryptamine). Dimethyltryptamine (DMT), 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), 5- MeO-DiPT (5-Methoxy-Diisopropyltryptamine), 4-AcO-DMT (4-Acetoxy- Dimethyltryptamine), DiPT (N,N-Diisopropyltryptamine), DET (Diethyltryptamine), 4- HO-MiPT (4-Hydroxy-N-Methyl-N-Isopropyltryptamine), 4-AcO-MiPT (4-Acetoxy-N- Methyl-N-Isopropyltryptamine), 5-MeO-MiPT (5-Methoxy-N-Methyl-N- Isopropyltryptamine), Bufotenin (5-hydroxy-N, N-dimethyltryptamine), 4-HO-MET (4- Hydroxy-N-Methyl-N-Ethyltryptamine), AMT (Alpha-Methyltryptamine), 4-HO-DiPT (4-Hydroxy-N,N-Diisopropyltryptamine) or any combination thereof.

7. The conjugate according to claim 6, wherein said tryptamine compound or precursor thereof is 4-HO-DiPT or a precursor thereof.

8. The conjugate according to claim 5, wherein the psychedelic compound or a precursor thereof is a phenethylamine compound or precursor thereof selected from thegroup consisting of Mescaline, 2C-B, DOx series, 3,4-methylenedioxymethamphetamine (MDMA) or a combination thereof.

9. The conjugate according to claim 5, wherein the psychedelic compound or a precursor thereof is a phenethylamine compound or precursor thereof is selected from the group consisting of N6-allyl-6-nor-lysergic acid diethylamide (AL-LAD), LSA, lysergic acid diethylamide (LSD)10. The conjugate according to any one of claims 1 to 9, wherein said NMDAR modulator or a precursor thereof is a NMDAR agonist or a NMDAR partial agonist.

11. The conjugate according to any one of claims 1 to 10, wherein said NMDAR modulator or a precursor thereof is one or more of glutamate, glycine, D-serine, L- aspartate, D-cycloserine, 1 -aminocyclopropane- 1 -carboxylic acid (ACPC), Sarcosine, Rapastinel, a precursor thereof or any combinations thereof.

12. The conjugate according to claim 11, wherein said NMDAR modulator or a precursor thereof is D-serine, D-cycloserine, a precursor thereof or any combinations thereof.

13. The conjugate according to any one of claims 1 to 12, wherein said at least one psychedelic compound or a precursor thereof is 4-HO-DiPT or a precursor thereof and said at least one NMDAR modulator or a precursor thereof is D-serine, D-cycloserine, a precursor thereof or any combinations thereof.

14. The conjugate according to any one of claims 1 to 13, having a structure of Formula Ila:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof,wherein K is a point of connectivity to at least one NMD AR modulator or a precursor thereof,Li is -(CH2)m- ,-C(O)-, -O-, -NH-, -O-CH2- -N-(CH2)m- -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6,Ri and R2are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, C1-C12 haloalkyl,R3, R4, Rs, Re is each independently from the other selected from hydrogen, deuterium, cyano, amino, amide, nitro, hydroxy, acetoxy, oxo, halo, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 haloalkenyl, C2-Ci2alkynyl, C2-C12 haloalkynyl, C1-C12 alkoxy, C1-C12 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, trifluoromethyl.

15. The conjugate according to any one of claims 1 to 13, having a structure of Formula lib:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein K is a point of connectivity to at least one NMD AR modulator or a precursor thereof,Li is -(CH2)m-,-C(O)-, -O-, -NH-, -O-CH2-, -N-(CH2)m-, -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6,Ri and R2 are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, C1-C12 haloalkyl,Ra, R4, Rs, Re is each independently from the other selected from hydrogen, deuterium, cyano, amino, amide, nitro, hydroxy, acetoxy, oxo, halo, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 haloalkenyl, C2-Ci2alkynyl, C2-C12 haloalkynyl, C1-C12 alkoxy, C1-C12 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, trifluoromethyl.

16. The conjugate according to claim 14 or 15, wherein at least one NMD AR modulator or a precursor thereof is D-serine, D-cycloserine, a precursor thereof or any combinations thereof.

17. The conjugate according to any one of claims 1 to 16, having a structure provided by Formula (Illa) or Formula Illb:or a pharmaceutically acceptable salt, solvate, hydrate, any stereoisomer thereof, an isotopologue or a physiologically functional derivative thereof, wherein Ri, R2, R3, R4, Rs, Re and Li are as defined above, L2 is -(CH2)t-,-C(0)-, -O-, -NH-, -O-CH2-, -N-(CH2)t-, or -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, t is selected from 0, 1, 2, 3, 4, 5 or 6.

18. The conjugate according to any one of claims 14 to 17, wherein Li is (i) -(CH2)m- , optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1 or 2, (ii) -(CH2)2-, optionally substituted with C1-C3 alkyl, (iii) -(CH2)2-, (iv) - (CH2)2-, optionally substituted with Ci alkyl or (iv) -(CH2)2.

19. The conjugate according to any one of claims 14 to 17, wherein L2 is -C(=O)-.

20. The conjugate of any one of claims 14 to 19, wherein R3, R4, R5, Re is each independently from the other selected from hydrogen, deuterium, hydroxy, acetoxy, Ci- C12 alkoxy.

21. The conjugate of any one of claims 14 to 20, having a structure provided by Formula Villa or Vlllb:or a pharmaceutically acceptable salt, solvate, hydrate, an isotopologue or a physiologically functional derivative thereof, wherein Ri and R2 are as defined above.

22. The conjugate of claim 21 wherein Ri and R2 are each, independently, H or Ci- Ce alkyl.

23. The conjugate of any one of claims 14 to 22, having a structure provided byFormula Xa or Formula Xb:

24. The conjugate of any one of claims 14 to 23, having a structure provided byFormula Xia or Formula Xlb:

25. The conjugate according to any one of claims 1 to 13, having a structure of Formula (XXIa)wherein Li is -(CH2)m- ,-C(0)-, -0-, -NH-, -O-CH2- -N-(CH2)m- -NH-C(O) , each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, m is selected from 0, 1, 2, 3, 4, 5 or 6,L2is -(CH2)t-, -O-C(=O)-, -C(=O)-, -O-, -NH-, -O-CH2-, -N-(CH2)t-, or -NH-C(O), each optionally substituted with C1-C12 alkyl, C1-C12 haloalkyl, or halo, t is selected from 0, 1, 2, 3, 4, 5 or 6,Ri and R2 are each independently from the other selected from H, hydroxyl, C1-C12 alkyl, C1-C12 haloalkyl,R7 if present, is independently hydrogen, deuterium, cyano, amino, amide, nitro, hydroxy, acetoxy, oxo, halo, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 haloalkenyl, C2-C12 alkynyl, C2-C12 haloalkynyl, C1-C12 alkoxy, C1-C12 haloalkoxy, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, trifluoromethyl, n is selected from 0, 1, 2, 3, or 4.

26. The conjugate according to any one of claims 1 to 13 and 25, wherein L2is -O- C(=O)-.

27. The conjugate according to any one of claims 1 to 13, 25 and 26, having a structure provided by Formula (XXIIa):wherein Ri and R2, Li and R7 are as defined above.

28. The conjugate according to any one of claims 25 to 27, wherein R7 if present, is independently hydrogen, deuterium, hydroxy, acetoxy, C1-C12 alkoxy.

29. The conjugate according to any one of claims 1 to 13 and 25 to 28, wherein said conjugate is characterized by the structure of Formula XXVa’:Wherein Rl and R2 are each, independently, H or Ci-Ce alkyl.

30. The conjugate according to any one of claims 1 to 13 and 25 to 29, wherein said conjugate is characterized by the structure of Formula XXVIa:

31. The conjugate according to any one of claims 1 to 13 and 25 to 30, wherein said conjugate is characterized by the structure of Formula XXVIIc:

32. The conjugate according to any one of claims 1 to 31 , having the chemical formula 4-(3-(2-(diisopropylamino)ethyl)-4-hydroxy-lH-indole-l-carbonyl)oxazolidin-2-one, 4- (3-(2-(diisopropylamino)ethyl)-4-hydroxyindoline- 1 -carbonyl)oxazolidin-2-one, 3-(2- (diisopropylamino)ethyl)-lH-indol-4-yl (3-oxoisoxazolidin-4-yl)carbamate or any combination thereof.

33. A composition comprising the conjugate of any one of claims 1-32.

34. The conjugate of any one of claims 1 to 32 or the composition of claim 33 for use in a method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder, the method comprising administering to said subject the conjugate or the composition.

35. The conjugate or the composition for use of claim 34, wherein said disease or disorder is schizophrenia, depression, post-traumatic stress disorder, obsessive- compulsive disorder (OCD), cerebral palsy, muscular dystrophy, spina bifida, spinal muscle atrophy (SMA), Parkinson's disease, epilepsy, amyotrophic lateral sclerosis (ALS), Ataxia, attention-deficit hyperactivity disorder, generalized anxiety disorder, or panic disorder, cervical dystonia, general dystonia, chorea, functional movement disorder, Huntington's disease, multiple system atrophy, myoclonus, chronic pain, inflammation, Parkinsonism, Alzheimer’s disease, sleep-wake disorders, Stroke or repeated head trauma, progressive supranuclear palsy, restless legs syndrome, tardive dyskinesia, Tourette syndrome, tremor, or Wilson's disease or an autism spectrum disorder (ASD) or a symptom thereof.

36. The conjugate of any one of claims 1 to 32 or the composition of claim 33 for use in a method of treating, reducing the incidence of, reducing the severity of or improvinga pathology of a subject with schizophrenia, the method comprising administering to said subject the conjugate or the composition.

37. A method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with a neuropsychiatric disease or disorder, neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder, the method comprising administering to said subject the conjugate of any one of claims 1 to 32, or the composition of claim 33.

38. The method of claim 37, wherein said disease or disorder is schizophrenia, depression, post-traumatic stress disorder, obsessive-compulsive disorder (OCD), cerebral palsy, muscular dystrophy, spina bifida, spinal muscle atrophy (SMA), Parkinson's disease, epilepsy, amyotrophic lateral sclerosis (ALS), Ataxia, attentiondeficit hyperactivity disorder, generalized anxiety disorder, or panic disorder, cervical dystonia, general dystonia, chorea, functional movement disorder, Huntington's disease, multiple system atrophy, myoclonus, chronic pain, inflammation, Parkinsonism, Alzheimer’s disease, sleep-wake disorders, Stroke or repeated head trauma, progressive supranuclear palsy, restless legs syndrome, tardive dyskinesia, Tourette syndrome, tremor, or Wilson's disease or an autism spectrum disorder (ASD) or a symptom thereof39. A method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with schizophrenia, the method comprising administering to said subject the conjugate of any one of claims 1-32, or the composition of claim 33.

40. A method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with depression, the method comprising administering to said subject the conjugate of any one of claims 1-32, or the composition of claim 33.

41. The method of claim 40, wherein said treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with depression comprises treatmentresistant depression.

42. A method of treating, reducing the incidence of, reducing the severity of or improving a pathology of a subject with post-traumatic stress disorder, the method comprising administering to said subject the conjugate of any one of claims 1-32, or the composition of claim 33.

43. A method of enhancing neuroplasticity in a subject with a neurologic disease or disorder, a neurocognitive disease or disorder, or a motor disease or disorder, the method comprising administering to said subject the conjugate of any one of claims 1-32, or the composition of claim 33.

44. The method of claim 43, wherein said disease or disorder is schizophrenia, depression, post-traumatic stress disorder, obsessive-compulsive disorder (OCD), cerebral palsy, muscular dystrophy, spina bifida, spinal muscle atrophy (SMA), Parkinson's disease, epilepsy, amyotrophic lateral sclerosis (ALS), Ataxia, attentiondeficit hyperactivity disorder, generalized anxiety disorder, or panic disorder, cervical dystonia, general dystonia, chorea, functional movement disorder, Huntington's disease, multiple system atrophy, myoclonus, chronic pain, inflammation, Parkinsonism, Alzheimer’s disease, sleep-wake disorders, Stroke or repeated head trauma, progressive supranuclear palsy, restless legs syndrome, tardive dyskinesia, Tourette syndrome, tremor, or Wilson's disease or an autism spectrum disorder (ASD) or a symptom thereof.

45. Use of the conjugate of any one of claims 1-32 for the preparation of a pharmaceutical composition.

Images