COMPOSITIONS AND METHODS OF USE COMPRISING SUBSTANCES WITH NEURAL PLASTICITY ACTIONS ADMINISTERED AT NON-PSYCHEDELIC / PSYCHOTOMIMETIC DOSAGES AND FORMULATIONS.

Abstract

Compositions and methods of use comprising serotonin (5-HT) receptor agonists and NMDAR modulating substances, including especially certain substances classified as 5-HT2A agonists currently described to exert NMDAR modulating effects, administered as neural plasticity modulators, at non-psychedelic / psychotomimetic dosages, posology and formulations, for the treatment of diseases and conditions and for the enhancement of functions (neuroplastics).

Description

COMPOSITIONS AND METHODS OF USE INCLUDING SUBSTANCES WITH NEURAL PLASTICITY ACTIONS ADMINISTERED AT NON-PSYCHEDELIC / PSYCHOTOMIMETIC DOSAGES AND FORMULATIONS CROSS REFERENCE WITH RELATED REQUESTS This application claims priority of and benefit from the filing date of the US Patent Application. No. 62 / 814,929, filed March 7, 2019, and US Pat. No. 62 / 844,151, filed May 7, 2019, the disclosures of which are incorporated by reference herein in their entirety. FIELD OF THE INVENTION Various aspects of the present invention relate to compositions and methods including substances that provide neural plasticity, and the administration of those substances at non-psychedelic and / or psychotomimetic dosages. BACKGROUND OF THE INVENTION The following sections are intended to introduce the reader to various aspects of the art that may be related to various aspects of the present invention, which are described and / or claimed below. This discussion is believed to be useful in providing the reader with background information to facilitate a better understanding of the various aspects of the present invention. Accordingly, it should be understood that these statements are to be read in this view and not as prior art admissions. Both the medical establishment and conventional wisdom define psychedelics, (including those in the triptan family, and including substances classified as 5-HT2A agonists), by their ability to determine certain alterations in consciousness, emotion, and cognition. , including positive and negative psychotomimetic symptoms (eg, psychedelic effects, psychedelic experience, psychotomimetic effects). These psychedelic / psychotomimetic effects are known to laymen and doctors for their potential recreational misuse and to researchers in the psychiatric field for their potential therapeutic uses in psychiatric and research applications for the study of brain function. In the case of substances in the triptan family, it is thought that these psychedelic / psychotomimetic effects are primarily induced by agonist actions at the 5-HT 2A receptor in the 5-HT receptor family. croaon / Lznz / q / υιλι Psychedelics are currently under investigation for the treatment of many psychiatric illnesses and symptoms, including depression, PTSD, OCD, addiction, anxiety associated with end-stage cancer. From the available scientific literature and other descriptions (including patents and patent applications), and from currently ongoing clinical studies, the psychedelic experience, which includes positive and negative psychotomimetic effects induced by a serotonin agonist substance, is an integral part of treatment. purported, research application, and even recreational misuses of these substances. Particularly for therapeutic purposes, serotonin agonist psychedelic drugs are administered in a private setting and preceded and followed by counseling and / or psychotherapy and the entire session is closely supervised and monitored (Johnson M, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20). According to researchers and therapists, to achieve therapeutic efficacy for certain psychiatric disorders, administration of the serotonin agonist at a dose that produces psychedelic and / or psychotomimetic symptoms should be paired with adjunctive therapies, including particular physical conditioning, as well as counseling and / or psychotherapy (talk therapy) before, during and after administration of the drug. The psychedelic experience (which includes disturbances in consciousness, emotion, and cognition, and positive and negative psychotomimetic symptoms) is thus viewed by researchers and scientists to date as an integral part of the potential therapeutic efficacy of psychedelic drugs. Psychedelics are generally administered once in a single session (single dose of a psychedelic substance) with acute psychedelic / psychotomimetic effects lasting approximately four to six hours. In addition to the acute effects, beneficial psychological effects lasting for months after a single session have been described and contribute to a current understanding of the potential beneficial effects of treatment with 5HT agonist drugs [ Griffiths RR, Richards WA, Johnson MW, McCann UD, Jesse R. Mystical-type Experiences Occasioned by Psilocybin Mediate the Attribution of Personal Meaning and Spiritual Significance 14 Months Later. J Psychopharmacol. 2008 Aug;22(6):621-32); Carhart-Harris RL, Roseman L, Bolstridge M, Demetriou L, Nienke J Pannekoek, Wall MB, Tanner M, Kaelen M, McGonigle J, Murphy K, Leech R, Curran HV, Nutt DJ. Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms Scientific Reports volume 7, Article number: 13187 (2017)]. The mechanisms underlying the potential efficacy of 5-HT2A agonists administered at high psychedelic / psychotomimetic dosages (single sessions) for depression have recently been linked to BDNF and mToR pathways and potentially related to neural plasticity ( Ly C, Greb AC, Cameron LP, et al. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018;23(ll):3170-3182.). croaon / Lznz / q / υιλι Selection of NMDAR antagonists (open channel blockers) have been found to be effective for neurological and psychiatric diseases (for example, memantine, amantadine, and a combination of dextromethorphan-quinidine are respectively approved by the FDA for dementia of Alzheimer's, Parkinson's disease, and emotional lability secondary to pseudobulbar palsy; and esketamine is FDA-approved for treatment-resistant depression). In addition, another NMDAR antagonist, dextromethadone, is under investigation for psychiatric disorders and for a multiplicity of diseases, syndromes, and neurological signs and symptoms (hereinafter defined as neuropsychiatric disorders) and ophthalmologic disorders, and metabolic disorders and disorders associated with aging ( U.S. Patent No. 9,468,611 and International Patent Application No. PCT / US2018 / 016159). Dextromethorphan in combination with bupropion is under investigation for depression and for agitation in dementia (Axsome Therapeutics). Additionally, there is mounting evidence for the actions of NMDAR antagonists, in particular ketamine and dextromethadone, in modulating neural plasticity (L¡ N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959-964. doi:10.1126 / sc¡ence.H90287; Vitolo OV, Manfredi PL, Inturrisi CE, DiGuglielmo G, Hanania T, Bernstein G, DeMartin S, Fogaca M, Duman R, Traversa S. Development of the N-Methyl-D-Aspartate Receptor (NMDAR) Antagonist d-Methadone (REL 1017) for the Treatment of Depression and Other CNS Disorders.American Society of Clinical Psychopharmacology annual meeting, May 2019;Fogaga MV, Fukumoto K, Franklin T, et al. N-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORCl-dependent antidepressant effects. Neuropsychopharmacology. 2019;44(13):2230-2238). Thus, the therapeutic potential of NMDAR antagonists at dosages that do not elicit psychedelic or psychotomimetic effects has been established for select drugs and select diseases (memantine, adamantine, and dextromethorphan / quinidine were FDA-approved, respectively, for Alzheimer's dementia, Parkinson's and emotional lability secondary to pseudobulbar palsy). To be appreciated, the recently FDA-approved dosage of esketamine for the treatment of depression remains high enough to cause some degree of psychedelic / psychotomimetic effects (dissociative effects) and at this time esketamine treatment is restricted to treating resistant depression and requires supervision in the doctor's office. In addition to appreciating, the mechanisms underlying the potential effects of 5-HT2A agonists for the treatment of depression (Ly et al., 2018), and the mechanism underlying the potential efficacy of NMDAR antagonists for a multiplicity of disorders. and conditions, both are thought to be dependent on MTorR and BDNF (International Patent Application No. croaon / Lznz / q / υιλι PCT / US2018 / 016159; De Martin S, VitoloOV, Bernstein G, Alimonti A, Traversa S, Inturrisi CE, Manfredi PL. The NMDAR Antagonist Dextromethadone Increases Plasma BDNF Levels in Healthy Volunteers Undergoing a 14-day In-Patient Phase 1 Study. ACNP annual meeting, December 9-13, 2018; Hollywood, Florida; L¡N, Lee B, Liu RJ, et al. mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science. 2010;329(5994):959-964. doi:10.1126 / science.1190287; Fogaga MV, Fukumoto K, Franklin T, et al. N-Methyl-D-aspartate receptor antagonist d-methadone produces rapid, mTORCl-dependent antidepressant effects. Neuropsychopharmacology. 2019;44(13):2230-2238). However, these mechanisms for inducing neural plasticity were taught to be distinct, one mechanism being mediated via 5-HT2A receptors and the other mechanism being mediated by the open channel block of NMDARs. BRIEF DESCRIPTION OF THE INVENTION Certain exemplary aspects of the invention are set forth below. It is to be understood that these aspects are presented solely to provide the reader with a brief summary of some forms the invention might take and that these aspects are not intended to limit the scope of the invention. In fact, the invention may cover various aspects that may not be explicitly stated below. One aspect of the present invention is directed to a compound comprising a structural analogue of psilocin, norpsilocin, psilocybin, baeocystin, norbaeocystin or N,Ndimethyltryptamine, according to formula I: crooon / Lznz / q / υιλι wherein (1) R1 and R2 are independently hydrogen, deuterium, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 (independently or nitrogen ring closure), aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino , alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (2) R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium , halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R4 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, any of which is optionally substituted on a or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano , nitrate; or R4 is selected from the group consisting of alkyl ester, formyl, hydroxy, arylamido, alkylamido, alkylcarbamoyl, arylcarbamoyl, amino, alkylsulfonyl, alkylamino; (4) R5 represents 13 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl , optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (5) R6 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl any of which is optionally substituted on one or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R6 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate, -OP(O)(OH)2, -OC(O)R7, -OSO2OH, -OC(O)NHR7, -OC(O)NR7R8 or -SONH; and (6) n is 1 to 5. Another aspect of the present invention is directed to a compound comprising a structural analogue of 2,5-Dimethoxy-4-iodoamphetamine, according to formula II: crooon / Lznz / q / υιλι croaon / Lznz / q / υιλι wherein (1) A is C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene; (2) R1 and R2 are independently hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 (independently or nitrogen ring closure), aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino , alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (4) R4 and R5 are, independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in a or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano , nitrate, or R4 and R5 are, independently for each occurrence, selected from the group consisting of alkyl ester, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitrate; and (5) R6 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl. C8, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl , alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Another aspect of the present invention is directed to a compound comprising a structural analogue of lysergic acid diethylamide, according to formula III: croaon / Lznz / q / υιλι where (1) R1 and R2 are, independently, hydrogen, deuterium, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 cycloalkenyl (independently or ring closure with nitrogen), aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (2) R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, optionally substituted in one or more positions by deuterium , halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R4 and R7 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro , cyano, nitrate; (4) R5 and R6 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, optionally substituted in a or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano , nitrate; or R5 and R6 are, independently for each occurrence, selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; and (5) R8 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl , alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Another aspect of the present invention is directed to a compound comprising a structural analogue of ibogaine, according to formula IV: croaon / Lznz / q / υιλι OR r3 wherein (1) R1 is deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, optionally substituted on one or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate ; (2) R2 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R2 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R3 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium , halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of alkyl ester, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitrate; and (4) R4 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl. C8, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl , alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Formulas I-IV also appear in Table 1A (below). Another aspect of the present invention is directed to a method of preventing or treating diseases and conditions or improving function in patients or subjects, the method comprising administration of a compound as described for Formulas I-IV at doses, dosages, posology, or formulations devoid of clinically significant psychedelic or psychotomimetic actions or effects, and having clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / mL or less, or human CNS 5-HT2A receptor occupancy of 50% or less, or PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes. Another aspect of the present invention is directed to a method for preventing or treating diseases and conditions or improving functions in patients or subjects, the method comprises the administration of a 5-HT2A agonist substance at doses, dosages, posology, or formulations devoid of clinically significant psychedelic or psychotomimetic actions or effects, and having clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / mL or less, or human CNS 5-HT2A receptor occupancy of 50% or less , or PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes. BRIEF DESCRIPTION OF THE DRAWINGS The accompanying drawings, which are incorporated into and constitute a part of this specification, illustrate embodiments of the invention and, together with the general description of the invention mentioned and the detailed description of the embodiments below, serve to explain the principles of the present invention. . Fig. 1A is a graph showing the effect of psilocybin on the oral glucose tolerance test. ***p<0.001; One-way ANOVA followed by Tukey's post-hoc test. Fig. IB is a graph showing the effect of psilocybin on the glycemic spike. ***p<0.001; One-way ANOVA followed by Tukey's post-hoc test. Fig. 2A is a graph showing body weight (pre-treatment with psilocybin). *P<0.05, **p<0.01; One-way ANOVA followed by Tukey's post-hoc test. Fig. 2B is a graph showing the effect of psilocybin on body weight (after treatment) at slaughter. *P<0.05, **p<0.01; One-way ANOVA followed by Tukey's post-hoc croaon / 1 znz / q / υιλι test. Fig. 2C is a graph showing the effect of psilocybin on liver weight (after treatment) at slaughter. *P<0.05, **p<0.01; One-way ANOVA followed by Tukey's post-hoc test. Fig. 3A is a photograph showing liver histology via H&E staining of liver tissue obtained from SD-fed rat, 10X magnification. Fig. 3B is a photograph showing liver histology via H&E staining of liver tissue obtained from a WD + vehicle rat, 10X magnification. Fig. 3C is a photograph showing liver histology via H&E staining of liver tissue obtained from a WD + psilocybin rat, 10X magnification. The Figs. 4A to 4C are graphs related to liver inflammation by showing gene expression of three interleukins involved in inflammatory pathways (Fig. 4A shows IL-6; Fig. 4B shows IL-10; Fig. 4C shows CCL2). ***p<0.001 and ****p<0.0001; One-way ANOVA followed by Tukey's post-hoc test. Fig. 5 is a graph showing the production of reactive oxygen species in rat livers. *p<0.05; One-way ANOVA followed by Tukey's post-hoc test. Fig. 6A is a graph showing GPAT4 gene expression in rat livers. **p<0.01, ***p<0.001 and ****p<0.0001; One-way ANOVA followed by Tukey's post-hoc test. Fig. 6B is a graph showing SREPB2 gene expression in rat livers. **p<0.01, ***p<0.001 and ****p<0.0001; One-way ANOVA followed by Tukey's post-hoc test. The Figs. 7A to 7C are graphs showing the results for a Locomotion Activity Test for crossbreeding (Fig. 7A), two-legged (Fig. 7B), and grooming (Fig. 7C). The Figs. 8A and 8B are graphs showing the plasma levels of two cytokines, TNF-α (Fig. 8A) and IL-6 (Fig. 8B), involved in inflammatory processes. *p<0.05 against rats fed Standard Diet, ##p<0.01 against rats fed Western Diet; One-way ANOVA followed by Tukey's post-hoc test. Fig. 8C is a graph showing neurogenesis in SVZ assessed by the number of K¡67 positive cells. The Figs. 9A to 9E are photographs showing the expression of NMDAR subunits and 5-HT2 receptor subtypes in ARPE-19 cells. Fig. 10 is a graph showing the cell viability of ARPE-19 cells after treatment with the NMDAR agonist L-glutamate alone (1 mM L-Glu) or in combination with the 5-HT2A agonist psilocin at different concentrations. . *P < 0.05 against control cells treated crooon / Lznz / q / υιλι with vehicle (one-way ANOVA followed by Dunnett's post-hoc test. The Figs. 11A to 11C are graphs showing NMDAR subunit protein expression (Fig. 11A showing NMDAR1; Fig. 11B showing NMDAR2A; Fig. 11C showing NMDAR2B). ***p<0.001 against control (untreated cells), ##p<0.01 against cells treated with 10 pM psilocin for 24 hours; One-way ANOVA followed by Tukey's post-hoc test. The Figs. 11D to 11F are graphs showing NMDAR subunit protein expression (Fig. 11D showing NMDAR1; Fig. 11E showing NMDAR2A; Fig. 11F showing NMDAR2B). **p<0.01 vs. control (untreated cells); One-way ANOVA followed by Tukey's post-hoc test. The Figs. 11G to 111 are graphs showing NMDAR subunit protein expression after co-incubation with psilocin and MK-801 (Fig. 11G showing NMDAR1; Fig. 11H showing NMDAR2A; Fig. 111 showing NMDAR2B). *p<0.05, ****p<0.0001 vs. control (untreated cells); One-way ANOVA followed by Tukey's post-hoc test. The Figs. 12A and 12B are graphs showing % protein expression of HT2 receptors (Fig. 12A showing 5-HT2A; Fig. 12B showing 5-HT2C). ##p<0.01 against cells treated with psilocin 10 μΜ for 24 hours; One-way ANOVA followed by Tukey's post-hoc test. Fig. 13A is a graph showing psilocin cytotoxicity in keratocytes. Fig. 13B is a graph showing psilocin cytotoxicity in human corneal epithelial cells (HCE). Fig. 14A is a graph showing the viability of corneal cells (keratocytes) in the presence of psilocin at different concentrations. Fig. 14B is a graph showing the viability of corneal cells (HCE cells) in the presence of psilocin at different concentrations. Fig. 15A is a photograph showing the expression of 5-HT2A in keratocytes. Fig. 15B is a photograph showing the expression of NMDAR1 in HCE. Fig. 15C is a photograph showing the expression of 5-HT2A in HCE. Fig. 15D is a photograph showing the expression of 5-HT2C in HCE. The Figs. 16A to 16D are graphs showing cytokine expression by keratocyte cells treated with U937-activated monocyte conditioned medium (CM) for 24h and cultured in the presence or absence of psilocin. Fig. 16A shows the expression of IL-Ιβ after 4, and 10 h of treatment with activated U937 CM. Fig. 16B shows the expression of IL8 after 4 and 10 hours of treatment with activated U937 CM. Fig. 16C shows the expression of IL12 after 4 and 10 hours of treatment with activated U937 CM. Fig. 16D shows the expression of TNF-α after 4 and 10 hours of treatment with activated U937 CM. croaon / Lznz / q / υιλι Fig. 17 is a graph showing VEGF expression by keratocyte cells treated with U937-activated monocyte conditioned medium (CM) for 24h and cultured in the presence or absence of psilocin, after 4, 10 and 24h of treatment with activated U937 CM. The Figs. 18A to 18D are graphs showing cytokine expression by HCE cells treated with U937-activated monocyte conditioned medium (CM) for 24h and cultured in the presence or absence of psilocin. Fig. 18A shows the expression of IL-Ιβ after 4, and 10 h of treatment with activated U937 CM. Fig. 18B shows the expression of IL-8 after 4 and 10 hours of treatment with activated U937 CM. Fig. 18C shows the expression of IL-12 after 4 and 10 hours of treatment with activated U937 CM. Fig. 18D shows the expression of TNF-α after 4 and 10 hours of treatment with activated U937 CM. Fig. 19A is a graph showing the results of the beta-gal assay in cells treated with d-methadone. Fig. 19B is a graph showing an anti-senescence effect observed with 1 Onm psilocin in combination with 1 Onm d-methadone with a 34% reduction in beta-gal positive cells. The Figs. 20A to 20D are photographs of cells without UVB induction. The Figs. 21A to 21D are photographs of cells with UVB induction but without treatment. The Figs. 22A to 22D are photographs of cells treated with lOnm d-methadone (Ο.ΟΙμΜ). The Figs. 23A to 23D are photographs of cells treated with d-methadone 500nm. The Figs. 24A to 24D are photographs of cells treated with 10nm d-methadone + 5nm psilocin. The Figs. 25A to 25D are photographs of cells treated with d-methadone 500nm + psilocin 5nm. The Figs. 26A to 26D are photographs of cells treated with 5nm psilocin. The Figs. 27A to 27D are photographs of cells treated with 1 Onm psilocin + 1 Onm dmethadone. Fig. 28A is a graph showing the effect of psilocin-carbamate on the body (pre-treatment and after treatment) at sacrifice. *P<0.05, Student's t-test for unpaired data. Fig. 28B is a graph showing the effect of psilocin-carbamate on liver weight (pre-treatment and after treatment) at slaughter. *P<0.05, Student's t-test for unpaired data. Fig. 29 is a graph showing the effect of psilocin-carbamate on glucose in crooon / 1 znz / q / υιλι blood. The Figs. 30A to 30C are graphs showing the results for a Locomotion Activity Test by crossing (Fig. 30A), standing on two legs (Fig. 30B), and grooming (Fig. 30C). The Figs. 31A through 31C are graphs showing the results for a Novel Suppressed Feeding Test by minutes to reach food (Fig. 31A), times to reach food (Fig. 31B), and food eaten within five minutes (Fig. 31C). The Figs. 32A to 32F are graphs showing the results of an olfactory adaptation / maladaptation test with non-social stimuli. Control (black line) and psilocin-carbamate treated (dashed line) mice. The Figs. 33A to 33F are graphs showing the results of an adaptation / maladaptation test with social stimulation. Control (black line) and psilocincarbamate-treated (dashed line) mice. Fig. 34 is a graph showing NMDAR1 protein expression after psilocin-carbamate treatment. The Figs. 35A to 35C are graphs showing protein expression of the three synoptic proteins PSD95, p70 and synapsin 1 after psilocin-carbamate treatment. DETAILED DESCRIPTION OF THE INVENTION One or more specific embodiments of the present invention will be described below. In an effort to provide a concise description of these modes, all features of an actual implementation cannot be described in the specification. It should be appreciated that in the development of any actual implementation, as in any engineering or design project, numerous implementation-specific decisions must be made to achieve developer-specific goals, such as compliance with system-related and business-related constraints. , which can vary from implementation to implementation. On the other hand, it should be appreciated that such a development effort may be complex and time consuming, but could nonetheless be a routine design, fabrication and manufacturing undertaking for those skilled in the art having the benefit of this disclosure. Definitions For the purposes of this description, the present inventors define diseases as human and veterinary diseases / disorders / syndromes / symptoms in their different stages, from preclinical stages to advanced stages, (including symptoms and signs of diseases, including prodromes and other manifestations of diseases). ). For the purposes of this description, the present inventors define symptoms as crooon / Lznz / q / υιλι manifestations of diseases as defined above. For purposes of this disclosure, the present inventors define conditions as underperformance relative to the individual's potential and goals in cognitive, motor, and social abilities and underperformance in the special senses relative to the individual's potential and goals. For purposes of this disclosure, the present inventors define functions as special sense functions (vision, smell, taste, hearing, and balance), including for vision enhancement. For the purpose of this description, the present inventors define aging as the accumulation of changes in a living being over time, leading to a deficit or deterioration in physical, psychological, and social abilities. The present inventors include in this definition accelerated aging and diseases due to physical and chemical factors, including environmental factors, toxins, and drugs, food and lack of nutrients, and vitamins and drug treatments. Osteoporosis as a form of bone aging is of particular relevance because of the known presence of NMDARs in osteoblasts and osteoclasts (Chenu C, Serre CM, Raynal C, Burt-Pichat B and Delmas PD (1998) Glutamate receptors are expressed by bone cells and are involved in bone resorption.Bone 22:295-299). For purposes of this disclosure, the present inventors define treatment as treatment and / or prevention, including primary and secondary prevention, and amelioration of conditions, symptoms, disorders, syndromes, and diseases. For the purpose of this description, the present inventors define neural plasticity as structural and functional changes in the nervous system that occur at any time during the life time, including neurogenesis, modulation of neuron or soma or neurite astrocyte size, shape and length. , synoptic plasticity, including synaptogenesis, synoptic strength, spinogenesis, loss of synoptic spines, pruning, changes in synoptic spine volume, changes in synaptic densities, including changes in specific synoptic proteins and pathways (including PD95, PD93, synapsin , GLUR1, including especially mRNA encoding the synoptic density protein and receptor subunits, including especially AMPAR and NMDAR protein subunits, and including modulation of the mTOR pathway and TrkB pathway and changes in receptor pathways. neurotrophic factors, including especially BDNF. For the purpose of this disclosure, the present inventors define neuroplastic drugs or neuroplastics as drugs with the potential to modulate neural plasticity, as defined above. For a neuroplastic drug to be potentially useful for the treatment of diseases and conditions, the drug must be safe and well tolerated and the modulating action on neural plasticity must occur in the absence of clinically significant side effects, croaon / Lznz / q / υιλι including, especially, in the absence of psychedelic / psychotomimetic effects. Neuroplastic drugs are to be administered at neuroplastic doses, dosages, posology, and / or formulations, as defined below. For the purpose of this description, the present inventors define neuroplastic doses and in particular neuroplastic doses of drugs classified as 5HT2A agonists, as a dose, dosage, posology or formulation, including modified-release formulations, of a substance with actions of 5-HT2A agonist and actions on neural plasticity, including modulation of NMDARs, that is well-tolerated, safe, when administered at doses, dosages, posology, and / or formulations, that do not elicit clinically significant psychedelic / psychotomimetic effects. Neuroplastic drugs modulate NMDARs via gene regulation by NMDAR subunits and gene regulation by trophic factors, including BDNF, at doses, dosages, posology, and / or formulation that do not cause clinically significant off-target effects, including without causing clinically significant alterations in consciousness, emotion, and cognition, including positive and negative psychotomimetic symptoms (psychedelic effects, psychedelic experience, psychotomimetic effects). The novel mechanism of action of neuroplastic drugs for their uses in the treatment of diseases and conditions proposed by the inventors consists in the differential down-regulation of excessive Ca2+ influx only through subtypes of hyperactive NMDARs (selective open channel block) A-D in selected cell populations and / or cellular networks. Blocking excessive Ca2+ influx reinstates cellular functions, including functions essential for physiologic neural plasticity (eg, mobilization and synthesis of synaptic proteins, including NMDAR subunits, and synthesis of neurotrophic factors, including BDNF). Description of Various Aspects of the Invention The present inventors now provide new experimental evidence showing NMDAR-modulating actions of neuroplastic 5-HT2A agonists (see Example 3, below). This experimental evidence points to the fact that neural plasticity of low doses of 5-HT2A agonists can occur, in the absence of psychedelic / psychotomimetic effects, and thus these psychedelic / psychotomimetic effects can be viewed as side effects rather than therapeutic effects (as is the case with some NMDAR antagonists). The potential therapeutic effects of substances in the triptan family (5-HT agonists, including 5-HT2A agonists), administered chronically, continuously, or intermittently, at dosages and formulations that do not elicit psychedelic / psychotomimetic effects, have not been explored. properly before. Although there is a limited body of scientific literature on the administration of low doses of psychedelics, the available scientific publications, to date, teach the contrary to the use of these agents for the crooon / Lznz / q / υιλι treatment of diseases. The findings of Anderson et al., (Anderson T, Petranker R, Rosenbaum D, Weissman CR, Dinh-Williams LA, Huí K, Hapke E, Farb ÑAS. Microdosing psychedelics: personality, mental health, and creativity differences in microdosers. Psychopharmacology (Berl). 2019 Jan 20) and the review and studies by Polito and Stevenson, 2019 (Polito V, Stevenson RJ (2019) A systematic study of microdosing psychedelics. PLOS ONE 14(2): e0211023. https: / / doi.org / 10.1371 / journal.pone.0211023). https: / / doi.org / 10.1371 / journal.pone.0211023), by emphasizing that the beneficial effects of low-dose psychedelics can be defined at best as a generic increase in psychological functions, teaches the opposite of use of small doses of psychedelic substances as neuroplastics for the treatment of diseases, including neurological or ophthalmological diseases or for deficits associated with aging and senescence or even for a generic improvement in cognitive function (nootropic effect). In particular, Polito and Stevenson conclude: The current findings suggest that popular considerations of the effects of microdosing may not match the long-term experience of microdiggers, and that promising avenues for future research are the impacts of microdosing on the better mental health, attention skills, and neuroticism. The study by Fadiman and Korb (Fadiman J, Korb S. Might Microdosing Psychedelics Be Safe and Beneficial? An Initial Exploration. J Psychoactive Drugs. 2019 Mar 29:1-5) suggests that microdosing was followed by improvements in moods negatives. These conclusions emphasize how current research approaches and understanding of psychedelic microdosing to this day remains confined to the psychiatric experimental arena, teaching the opposite of the potential uses of 5-HT antagonist substances at dosages devoid of effects. psychedelics as neuroplastics for the treatment and prevention of neurological and ophthalmological diseases and metabolic diseases and other clinical indications and conditions listed in this application, including the treatment of psychiatric disorders as defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5 ). The potential for the treatment of mental disorders is not anticipated by a potential improvement in negative mood states as hypothesized by Fadiman. Furthermore, current knowledge of non-psychedelic / psychotomimetic dosages of 5-HT agonists teaches the opposite of their uses for therapeutic indications, including psychiatric indications: the potential efficacy of 5-HT agonists for the treatment of diseases, and specifically psychiatric illnesses, is currently entangled with its abilities to elicit psychedelic / psychotomimetic symptoms. The potential therapeutic efficacy of psychedelics currently under investigation thus remains within the limits of their ability to elicit the psychedelic experience and psychedelics are administered in a single dose, along with psychotherapy and counseling / talk therapy croaon / Lznz / q / υιλι pre, during and post-administration of the drug, in special facilities, under close supervision, for the treatment of certain diseases and psychiatric symptoms. Psychedelics administered in such a specific manner are currently in different stages of development, including in phase 2 clinical studies. The potential for 5-HT agonists for the treatment of diseases and conditions and aging at dosages that do not elicit psychedelic / psychotomimetic effects is not currently under clinical investigation and the teachings of current scientific knowledge teach the contrary of the therapeutic uses of 5-HT2A agonists at non-psychedelic / psychotomimetic dosages. Patients particularly sensitive to the mind-altering and psychedelic / psychotomimetic effects of 5-HT2A agonists may benefit from neuroplastic 5-HT2A agonists including modified-release (MR) formulations as detailed below, so that the 5-HT2A agonist can potentially be administered repeatedly for days or months or even chronically, without the need for a particular facility or the need for counseling and / or psychotherapy, or the need for close monitoring and supervision because psychedelia / psychotomimetics will not occur with the appropriate dosage and formulation. Repeated administration of 5-HT2A drugs over time, days to months, or chronically, continuously, or intermittently potentially allows for effective treatment of conditions, symptoms, disorders, syndromes, and diseases that may benefit from induction of neural plasticity, especially in patients for whom repeated induction of psychotomimetic and psychedelic effects may be contraindicated or may be detrimental. The therapeutic window for psilocybin and other 5-HT2A agonist drugs could be widened by changing the drug formulation to modified-release, as described in more detail below. Of interest, the present inventors also present experimental evidence that intermittent repeat therapy, including intermittent chronic therapy, eg, every other day, every three days, every week, every two weeks, every three months, may offer advantages over regular therapy. continuous chronic (daily therapy). The 5-HT2A agonist administered chronically at low, non-psychedelic doses (neuroplastic doses), may therefore be therapeutic for a multiplicity of diseases and conditions, not just psychiatric indications, which are the focus of researchers studying the psychedelic dosages of 5-HT2A agonists. There may be potential reciprocal allosteric effects with potential synergy of effects between selected molecules in these two drug classes, as shown by some of the novel experimental work detailed below. The present inventors therefore disclose that for many patients who could benefit from 5-HT receptor agonist neural plasticity effects, in croaon / 1 znz / q / υιλι particularly for patients who potentially benefit from the effects of Neural plasticity maintained over time, the psychedelic and psychotomimetic experience, and other harmful side effects of these drugs are problematic and harmful side effects of relative drug overdose and not intrinsic therapeutic activity, as seen by ongoing research activities. in the field of 5-HT2A agonists. In summary, drugs or drug formulations, with neural plasticity effects but devoid of psychedelic effects, could benefit patients and individuals and ameliorate or prevent conditions, symptoms, disorders, syndromes, and diseases in human subjects. In addition, a private facility and close personal supervision / counseling / psychotherapy for the actions of 5-HT2A agonists on neural plasticity are unnecessary when psychedelic formulations and dosages are not administered. The present inventors describe potential benefits of these compositions and novel uses of 5-HT2A agonists for the treatment of a multiplicity of conditions, symptoms, disorders, syndromes, and diseases, including ophthalmologic, neurologic, psychiatric, metabolic, and deficit treatments. associated with aging. Although psychedelic drugs by their very definition have psychedelic / psychotomimetic effects and their potential intended therapeutic benefits for psychiatric disorders are intrinsically linked to these psychedelic / psychotomimetic effects, and their therapeutic uses, currently under investigation, focus on psychiatric diseases and conditions that may benefit from the psychedelic experience, which is generally induced in single sessions with high-dose 5-HT agonists in a private facility and preceded and followed by psychological counseling and / or therapy (Griffiths RR, Richards WA, Johnson MW, McCann UD, Jesse R. Mystical-type Experiences Occasioned by Psylocibin Mediate the Attribution of Personal Meaning and Spiritual Significance 14 Months Later.J PsychopharmacoL 2008 Aug;22(6):621-32). The compositions and uses described in the current application are instead characterized by their ability to modulate neural plasticity as outlined above, at dosages and formulations that do not elicit psychedelic / psychotomimetic effects, and are administered in repeated doses over time, daily or intermittently, for periods of many days to months, or even chronically, to be potentially therapeutic for a multiplicity of conditions, symptoms, disorders, syndromes, and diseases, including those that require ongoing, days to months, or even chronic modulation of the neural plasticity, including neuropsychiatric, metabolic, and ophthalmologic conditions, symptoms, disorders, syndromes, and diseases. Thus, in the case of 5HT2A neuroplastics, the psychedelic effects are not therapeutic effects but are unwanted side effects, and these side effects make these drugs contraindicated for patients and subjects who might otherwise benefit from the neural plasticity actions of these drugs. drugs. croaon / Lznz / q / υιλι The posology, including dosage and frequency and schedule of administration (dosages), the formulations, including modified-release formulations, the duration of therapy, days or chronically opposed to once, and in certain cases the route and methods of administrations, and thus PK parameters (in particular Cmax, Tmax) and PD parameters, acute or chronic receptor occupancy, receptor downregulation effects, and downstream effects, including trophic effects on cells including effects on neurogenesis, promotion arborization, neurite outgrowth, synaptogenesis, synoptic reinforcement, spinogenesis, increase in synoptic spine volume, increase in synoptic densities, including modulation of specific synoptic proteins, including PD95, synapsin, GLUR1, including especially mRNA, and protein subunits of the different subtypes of NMDARs, subunits and subtypes of AMPARs, and including modulation of the mTOR pathway and TrkB pathway and modulation of neurotrophins, including BDNF, including anti-inflammatory effects, including effects on TNF-α, IL-10, IL-6 and other markers of inflammation and markers of neural plasticity described in the present inventors' experiments, in neurons, astrocytes, oligodendrocytes, Schwann cells, and potentially exerts trophic effects on selected additional cells, e.g., including especially cells of retinal pigment and other cells that support sensory receptors, including auditory, vestibular, olfactory, taste and tactile receptors, and finally the clinical effects, are very different. Furthermore, the adjunctive therapies and precautions associated with the treatment and, finally, the clinical indications and therapeutic indications probably differ substantially from the current uses and misuses by researchers, therapists and laymen. Based on the present inventors' observations and findings, the present inventors describe that for many patients and for a multiplicity of conditions, symptoms, disorders, syndromes, and diseases, the psychedelic experience and psychotomimetic effects are secondary effects of an overdose of substances with potential neuroplastic effects that are therapeutic at lower, non-psychedelic doses. Furthermore, while psychedelic effects / psychotomimetic effects may be therapeutic for select indications and select patients and under certain circumstances, outside the scope of this description, such as by subsets of patients suffering from disorders currently under investigation with psychedelics (depression, PTSD , anxiety, addiction), the present inventors describe that for a multiplicity of conditions, the symptoms, disorders, syndromes and diseases that can benefit from neuroplastic effects, including subsets of patients suffering from the same psychiatric disorders (depression, PTSD, anxiety, addiction), (the full list of these potential indications are described below), psychedelic experience / psychotomimetic effects are side effects of overdose of drugs given at super-therapeutic doses. For further clarification, the psychedelic experience and psychotomimetic symptoms are generally caused by croaon / Lznz / q / υιλι overdoses with 5-HT2A agonist and / or NMDAR antagonist neuroplastics, while the therapeutic effects of neuroplastics are exerted by much lower doses and safer (approximately 1 / 10th) of the same drugs and these neuroplastic effects, in the absence of psychedelic effects, and are potentially therapeutic for a multiplicity of conditions, symptoms, disorders, syndromes, and diseases as listed below. Furthermore, the tolerability, safety, and efficacy of select neuroplastics can be increased by novel MR formulations. The present inventors herein describe the potential neuroplastic actions of serotonin agonist substances, in particular substances with actions at the 5-HT2A receptor and other serotonin receptors, in particular psilocin-carbamate, psilocybin and baeocystin and their derivatives. Additionally, the present inventors describe the neuroplastic actions of psilocin, norpsilocin, norbaeocystin and their derivatives at doses and formulations that do not cause psychedelic or psychotomimetic symptoms. In addition, the present inventors describe the potentially therapeutic actions of select Structurally Modified Serotonin neuroplastic derivatives (SMSNs, including nitro-derivatives of 5-HT2A receptor agonists, as described below) as having neuroplastic effects, consistent with the definition of neuroplastic outlined above. These neuroplastic effects may be modulation of glutamate receptor transcription and synthesis, as described in the present inventors' novel experiments, and may be secondary to or facilitated by anti-inflammatory actions in neural and other mammalian tissues, thus new as indicated by the experiments of the present inventors. These neuroplastic effects may be of particular importance in preventing, alleviating, and treating a multiplicity of conditions, symptoms, disorders, syndromes, and diseases at dosages and formulations that do not produce psychedelic effects, or psychotomimetic effects, or other clinically significant side effects on thought, emotion, and cognition. Thus, in the case of neuroplastics, psychedelic and psychotomimetic effects are side effects and not therapeutic effects, while their potential effects on learning, including school / academic learning, motor and social skills learning, and emotional pathway dysfunction influenced by learning, are instead potentially therapeutic agents. The present inventors therefore describe that in the case of neuroplastics, not only effects on neural plasticity, but also cell trophic effects and anti-inflammatory effects, when following the appropriate dosages and formulations and posology, are present in the absence of symptoms. psychedelics / psychotomimetics, and furthermore the present inventors describe that neuroplastic effects, in addition to improving neuropsychiatric, metabolic and ophthalmological symptoms, diseases and conditions, may result in improvement in various functions, including sensory functions, including vision, and that these improvements may last crooon / 1 znz / q / υιλι longer than the pharmacological action at the 5-HT2A receptor and other receptors, that is, the therapeutic effects are due to their effects on neural plasticity and therefore the therapeutic effects of these drugs they may be present and sustained after virtually all of the clinically active activity of the drug has been eliminated. The present inventors further disclose that multiple doses, over the course of days or months, rather than single doses, are required for the treatment of a multiplicity of diseases and conditions (eg, 1-4 doses per day over 2-3 or more days or weeks or months or indefinitely or even a dose every 2 days or every 3 days or every week or every two weeks or every three months for many weeks or months or indefinitely); Different indications are likely to require different dosing, but treatment of chronic conditions, symptoms, disorders, syndromes, and diseases that may benefit from drugs that modulate neural plasticity are likely to require repeated administration over time of non-psychedelic / psychotomimetic formulations and dosages. , as shown in the experimental work of the present inventors. In selected circumstances, administration of a single non-psychedelic psychotomimetic dose of neuroplastic, eg, intranasally for social anxiety or for panic attack or for acute improvement of vision, may be helpful. The potential therapeutic and beneficial effects of neuroplastic drugs for the treatment of a multiplicity of conditions, symptoms, disorders, syndromes and diseases are however potentially due to continuing effects over time on neural plasticity and other trophic and anti-inflammatory actions. of neuroplastics administered in multiple doses for prolonged periods (days to months or chronically). The effects of certain 5-HT2A agonists given at multiple doses repeated over time, intermittently (for example, every other day or every 3 days or every third week), or continuously (for example, daily or many times a day) at dosages and formulations that do not cause psychedelic symptoms, by combining effects of neural plasticity, trophic effects on neurons and other cells, and anti-inflammatory actions, are potentially useful for the treatment of a multiplicity of conditions, symptoms, disorders, syndromes, and diseases, including for the improvement of functions, including ophthalmological, neurological, psychiatric and metabolic diseases and for the treatment of aging including senescence and deficits associated with aging, including accelerated aging and senescence induced by noxious agents, including medical treatments, including cancer treatments, including chemotherapy and therapy of radiation, including the enhancement of special senses (vision, smell, taste, hearing and balance) and in particular to improve vision in eye diseases (eg macular degeneration) and brain diseases (eg CVA) and to improve the vision in subjects with normal visual acuity (improved visual acuity). The present inventors' novel experimental and observational work crooon / 1 znz / q / υιλι outlined below and the present inventors' description of neuroplastic drugs, uncovers the potential of substances and drugs that act via 5-HT2A receptors. , and that they also potentially act via other serotonin receptors and other receptors and transporters (DAT, NET, SERT) and other mechanisms, including other 5-HT receptors, DA receptors, and sigma receptors, CB1, NOP for the treatment of a multiplicity of diseases and conditions, including ophthalmological, neurological, psychiatric and metabolic diseases and for the treatment of aging including senescence and deficits associated with aging, including accelerated senescence induced by noxious agents, including medical treatments, including deficits of special senses (vision, smell, taste, hearing and balance) caused by aging, drug treatments or other causes. Of particular importance are drugs that act on both the 5-HT system and the glutamate system, in particular 5-HT2A agonists and antagonists of open-channel NMDAR, glutamate receptors, including AMPARs, and or S-nitrosylation activity. at the NMDAR receptor. Modulation of neural plasticity, anti-inflammatory actions, and neuroprotective and trophic actions in the retina, olfactory, and inner ear, including supporting cells, including retinal pigment cells, and cells of the nervous system, including neurons, astrocytes, and oligodendrocytes and Schwann cells are potential mechanisms and targets for the therapeutic actions of neuroplastic substances and drugs, as detailed throughout this application. The therapeutic actions listed above are obtained especially with neuroplastic drugs that act mainly as 5-HT2A receptor agonists administered repeatedly, continuously or intermittently, over the course of days or months or chronically. Indolamines and phenethylamines, particularly psilocybin, administered in single sessions at doses that elicit psychedelic symptoms, are currently under clinical investigation for a multiplicity of psychiatric illnesses and symptoms. Depression, anxiety, PTST, end-of-life distress, and addiction are some of the psychiatric illnesses and symptoms that can be ameliorated by psychedelics [Kvam TM, Stewart LH, Andreassen OA. Psychedelic drugs in the treatment of anxiety, depression and addiction. Tidsskr Ñor Laegeforen. 2018 Nov 12; 138(18)]. Despite the renewed interest of the scientific psychiatric community in 5-HT2A agonists for the treatment of psychiatric indications, the recreational abuse of these substances and drugs poses a significant barrier to their development as pharmaceutical compounds. There remain strong public safety and regulatory concerns about the use of substances with the potential to induce psychedelic effects, including concerns for their uses as disease treatment, and these substances and drugs remain illegal in most countries. In the U.A.E. and in many other countries, psychedelics, natural and synthetic, including plants and mushrooms, are classified as Schedule I substances with high potential for croaon / Lznz / q / υιλι abuse and no clinical uses. Although the relative safety and low addiction potential of these substances have been emphasized in recent scientific publications (Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, Thomas CD, Hetzel SJ, Henriquez KM, Ribaudo AS , Hutson PR. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clin Pharmacokinet. 2017 Dec;56 (12): 1543-1554; Studerus E, Kometer M, Hasler F, Vollenweider FX. Acute, subacute and long-term subjective Effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol. 2011 Nov;25(ll): 1434-52; Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology. 2018 Nov; 142:143-166), due to their potential for abuse, which remains a concern despite the low potential for addiction, and due to strong and multi-faceted social barriers. -Cultural and legal (which vary widely across countries), the development of psychedelics for the treatment of disease remains problematic today, and further studies are needed to better define the role of these substances as therapeutic agents. Furthermore, current popular and scientific understanding teaches that psychotomimetic effects and or the holistic psychedelic experience are integral to the potential therapeutic activity of these substances. Although the importance of the psychedelic experience as a therapeutic tool may hold promise for some psychiatric indications and for subsets of patients, the present inventors disclose that dosages, posology, and formulations of 5-HT2A agonists administered repeatedly, chronically, or intermittently, for days or months, defined here as neuroplastics of 5-HT, as its actions on neural plasticity in the absence of psychotomimetic / psychedelic effects, and the potentially psychotomimetic free effects of novel chemicals with actions of neuroplastics, specifically neuroplastics of Synthetically modified serotonin agonists (SMSNs), also described in this application, may be therapeutic for diseases and conditions of the nervous system, including deficits of special senses, including ophthalmological, olfactory and inner ear conditions and a multiplicity of neurological conditions and diseases, psychiatric, ophthalmological and metabolic, and for the treatment of deficits associated with aging and senescence and for the improvement of cognition (nootropic effects) and social skills, motor skills and for the improvement of vision, smell, taste, hearing and balance and including for the improvement of vision in subjects with inadequate visual acuity in relation to their potential or preference. Apart from describing that at least one mechanism (modulation of BDNF and mToR-dependent pathways) to induce neural plasticity is shared by NMDAR antagonists, Fogaga et al., 2019 (dextromethadone), and 5-HT2A agonists, Ly et al., 2018 (5-HT2A agonists), the present inventors conducted an extensive review of the literature and found the following crooon / Lznz / q / υιλι reports pointing to possible interactions and overlapping actions between 5-HT2A agonists and NMDAR open channel blockers. The following reports, taken together with the present inventors' observations and experimental results (including Example 3) support the present application: First, certain 5-HT2A agonists were found to inhibit NMDA receptor activity (Arvanov VL, Liang X, Russo A, Wang RY. LSD and DOB: interaction with 5-HT2A receptors to inhibit NMDA receptor-mediated transmission in the rat prefrontal cortex, European Journal of Neuroscience, Vol. A Comparative Binding and Modeling Study. Current Medicinal Chemistry, 2012, 19, 3044-3057). When combined with the descriptions and experimental findings of the present inventors, the results by Arvanov et al., suggest that a complementary and synergistic action on the two drug targets could potentially increase biological responses, such as neural plasticity, and thus influence behavioral outcomes. therapeutic results for a multiplicity of diseases and conditions. Second, a study by Ceglia et al. (Ceglia I, Carli M, Baviera M, Renoldi G, Calcagno E. The 5-HT2A receptor antagonist M100,907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC. Journal of Neurochemistry , 2004, 91, 189-199) suggests that 5-HT2A antagonists prevent NMDAR blocking effects which may suggest that 5-HT2A receptor activation may be required for NMDAR antagonist actions: this finding also is potentially supportive of the present inventors' findings and disclosures for allosteric interactions and possible synergy between NMDA antagonists and serotonin agonists. Third, a 1998 report by Farber et al., (Farber NB, M.D., Hanslick J, Kirby C, McWilliams L, Olney JW. Serotonergic agent that activate 5-HT2A receptors prevent NMDA antagonist neurotoxicity. Neuropsychopharmacology 1998-Vol. 18, No. 1) suggests a potential protective action of β 5-HT52A agonists against toxicity induced by the high affinity NMDAR antagonist MK-801. This finding together with the present inventors' disclosure suggests a potential safety advantage for simultaneous administration of agent with 5-HT agonist actions and agents with NMDAR antagonist action. Fourth, work by Zhong et al. (Zhong P, Yuen EY, Zhen Yan. Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex. Mol Cell Neurosci. 2008 June; 38(2): 290-299) suggests that Effects of 5-HT2A receptor agonists on neuron membrane depolarization is dependent on NMDA receptors, suggesting a co-dependence on these receptors for at least part of their effects. And fifth, metabotropic glutamate receptors interact with 5-HT2A croaon / Lznz / q / υιλι receptors to form functional complexes in the cerebral cortex (González-Maeso J, Ang RL, Yuen T, et al. Identification of a serotonin / glutamate receptor complex implicated in psychosis. Nature. 2008;452(7183):93-97. doi:10.1038 / nature06612). Based on the combination of the observations by the authors cited above, suggesting indirect interactions between the serotonin receptor and NMDAR pathways, the present inventors hypothesized and then experimentally demonstrated a direct action of 5-HT2A in NMDAR modulation. ie, the induction by 5-HT2A agonists of the synthesis of NMDAR subunits in ARPE-19 cells. This novel finding and other experimental results detailed in Examples 1 to 3, below, unexpectedly point to the potential efficacy of 5-HT2A agonists not only when administered as single long-pulse doses for the treatment of depression and other prichiatric indications, according to the hypotheses formulated by many investigators (phase 2 studies are in progress), but also when administered as neuroplastics (at doses devoid of psychedelic / psychotomimetic effects), chronically, continuously or intermittently, for the treatment of diseases and conditions for where the modulation of NMDARs is potentially therapeutic, such as the diseases and conditions described in International Patent Application No. PCT / US2018 / 016159, and in the current application. Furthermore, the present inventors disclose that novel drugs with both 5-HT2A agonist actions and NMDAR antagonist actions may offer additional efficacy and safety compared to the combination of two agents. The present inventors have therefore designed a first set of 5-HT2A-affinity serotonergic agonists that contain novel molecular features that may confer additional modulatory activity on NMDARs. For this purpose, among others, the present inventors designed novel 5-HT agonists characterized by the introduction of a nitric acid ester group and plan to test the effects of these novel molecules for their affinity to block NMDAR subtypes in addition to their agonist effects at 5-HT2A receptors. The postulated mechanism for the NMDAR antagonistic actions of these novel compounds is modulation of NMDA receptor activity by S-nitrosylation of the sulfhydryl group of the cysteine ​​residue at the N-terminus (or extracellular domain) of NMDAR, while maintaining NMDAR activity. serotonergic of the parent compounds. The present inventors are in the process of testing these novel agents for both serotonergic activity in select 5-HT receptor families and subtypes as well as NMDARs and their subtypes. These novel compounds are also under test for their ability to prevent excitotoxicity, inflammatory cell damage, and for neurotrophic effects. Table 1A (below) includes modifications of psilocybin, psilocin, DMT, DOI, and LSD (5-HT2A agonists) to obtain novel derivatives with novel and improved pharmacokinetic (PK) and croaon / 1 znz / q / υιλι parameters and / o Pharmacodynamics (PD) and in particular deuterated derivatives to modulate PK and / or PD, fluoro derivatives to modulate lipo-solubility / permeability of the cell membrane and thus PK and PD properties, nitro derivatives to modify PK and PD parameters and potentially provide additional neuroprotective actions, including further modulation of NMDAR, and combinations thereof, including deuterated fluoro-nitro cerivates. crooon / Lznz / q / υιλι TABLE 1A Formula I of Table 1A represents a structural analog to psilocin, norpsilocin, psilocybin, baeocystin, norbaeocystin, or Ν,Ν-dimethyltryptamine, wherein (1) R1 and R2 are independently hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3C8 cycloalkenyl (independently or ring closure with nitrogen), aryl or heterocyclyl, optionally substituted on a or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (2) R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3 cycloalkenyl C8, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl , alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R4 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, any of which is optionally substituted on a or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano , nitrate; or R4 is selected from the group consisting of alkyl ester, formyl, hydroxy, arylamido, alkylamido, alkylcarbamoyl, arylcarbamoyl, amino, alkylsulfonyl, alkylamino; (4) R5 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl , aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (5) R6 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl any of which is optionally substituted on one or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R6 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate, -OP(O)(OH)2, -OC(O)R7, -OSO2OH, OC(O)NHR7, -OC(O)NR7R8 or -SONH; and (6) n is 1 to 5. Formula II of Table 1A represents a compound comprising a structural analogue of 2,5-Dimethoxy-4-iodoamphetamine, wherein (1) A is C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene ; (2) R1 and R2 are independently hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 (independently or nitrogen ring closure), aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino , alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R3 is hydrogen, deuterium, C1-C8 alkyl, C2 alkenyl croaon / Lznz / q / υιλι C8, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl , aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (4) R4 and R5 are, independently, hydrogen, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, optionally substituted in one or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate , or R4 and R5 are, independently for each occurrence, selected from the group consisting of alkyl ester, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitrate; and (5) R6 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl , alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Formula III of Table 1A represents a structural analog to lysergic acid diethylamide, wherein (1) R1 and R2 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 cycloalkenyl (independently or ring closure with nitrogen), aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (2) R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R4 and R7 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, crooon / Lznz / q / υιλι optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (4) R5 and R6 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, optionally substituted in a or more positions for deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano , nitrate; or R5 and R6 are, independently for each occurrence, selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; and (5) R8 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl , alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Formula IV of Table 1A represents a structural analog of ibogaine, wherein (1) R1 is deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl. C8, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl , alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (2) R2 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl, or heterocyclyl, optionally substituted in one or more positions by deuterium , halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R2 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; (3) R3 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium , halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate; or R3 is selected from the group consisting of alkyl ester, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitrate; and (4) R4 represents 1croaon / Lznz / q / υιλι substituents selected from the group consisting of hydrogen, deuterium, halogen, C1C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C1-C8 cycloalkenyl. C3-C8, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl , thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Another aspect of the present invention may involve the molecules described in Table 1A for the treatment of diseases and conditions in mammals with the NMDARs used in accordance with the following method to prevent and treat diseases and conditions or improve functions in patients or subjects, the method comprises the repeated administration of the substances from Table 1A or Table IB (below) at doses, dosages, posology, and / or formulations devoid of clinically significant psychedelic / psychotomimetic actions (neuroplastic dysis) and with clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / mL or less and or human CNS 5-HT2A receptor occupancy of 50% or less and preferably results in PD effects comparable to those exerted by human plasma psilocin Cmax of 2 ng / mL or less and or 5-HT2A human CNS receptor occupancy of 40% or less and preferably results in PD effects comparable to those exerted by human plasma psilocin Cmax of 1 ng / mL or less and or human CNS receptor occupancy of 5HT2A of 30% or less and / or in PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes and preferably in excess of 120 minutes and preferably in excess of 180 minutes. This method can occur where the administration of the substance occurs under conditions that can modulate the NMDARs and their subunits in addition to modulating the 5-HT2A receptors; where administration of the substance may provide protection from excitotoxicity; wherein administration of the substance can modulate neurogenesis; wherein administration of the substance occurs under conditions effective for the substance to exert neuroplastic effects, including modulation of neural plasticity; wherein the administration of the substance is safe and well tolerated, and, in particular, is devoid of clinically significant psychedelic and / or psychotomimetic effects; where the administration of the substance is repeated over days or months or is chronic; wherein the administration of the substance is intermittent and occurs every second day, every third day or every third week or every 2 weeks or every third month; and / or where blister pack or other suitable packaging is used in order to facilitate compliance when intermittent (non-daily) administration is used. Another aspect of the invention may include a method of preventing and treating diseases and conditions or improving functions in patients or subjects, the method comprising the crooon / Lznz / q / υιλι repeated administration of 5-HT2A agonist substances at doses, dosages, dosage, and o formulations devoid of clinically significant psychedelic / psychotomimetic actions (neuroplastic doses) and with clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / mL or less and o human CNS 5-HT2A receptor occupancy of 50% or less and preferably results in PD effects comparable to those exerted by human plasma psilocin Cmax of 2 ng / mL or less and or 5HT2A human CNS receptor occupancy of 40% or less and preferably results in PD effects comparable to those exerted by human plasma psilocin Cmax of 1 ng / mL or less and or 5-HT2A human CNS receptor occupancy of 30% or less and / or in PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes and preferably in excess of 120 minutes and preferably in excess of 180 minutes; This method can occur where the administration of the substance occurs under conditions that can modulate the NMDARs and their subunits in addition to modulating the 5-HT2A receptors; where administration of the substance may provide protection from excitotoxicity; wherein administration of the substance can modulate neurogenesis; wherein administration of the substance occurs under conditions effective for the substance to exert neuroplastic effects, including modulation of neural plasticity; wherein the administration of the substance is safe and well tolerated, and, in particular, is devoid of clinically significant psychedelic and / or psychotomimetic effects; where the administration of the substance is repeated over days or months or is chronic; wherein the administration of the substance is intermittent and occurs every second day, every third day or every third week or every 2 weeks or every third month; and / or where blister pack or other suitable packaging is used in order to facilitate compliance when intermittent (non-daily) administration is used. Another aspect may include a method of preventing and treating diseases and conditions in a subject, the method comprises administering 5-HT2A agonist derivatives, including carbamate derivatives, fluoro derivatives and including nitro derivatives and their deuterated versions including carbamate derivatives deuterated, deuterated fluoro derivatives and including nitro derivatives and deuterated fluoro derivatives, including substances listed in Table 1A and Table IB. Either method may include treatment of metabolic syndrome and its complications; treatment of impaired glucose tolerance, diabetes and its complication; treatment of NAFL, NAFLD, NASH and their complications; the treatment of obesity and its complications; the treatment of vision impairment and visual loss including macular degeneration and retinopathies; the treatment of neurological diseases, including neurodevelopmental diseases and neurodegenerative diseases that may benefit from modulation of croaon / Lznz / q / υιλι neural plasticity, including: Neurological diseases and their symptoms and signs that may respond to neuroplastic drugs and SIDS include: Alzheimer disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, including mild cognitive impairment associated with aging and chronic disease and its treatment, including chemotherapy, immunotherapy and radiation therapy, Parkinson's disease and related Parkinsonian disorders including but not limited to Parkinson's dementia; disorders associated with the accumulation of amyloid beta protein (including but not limited to cerebrovascular amyloid angiopathy, posterior cortical atrophy); disorders associated with accumulation or disruption of tau protein and its metabolites including but not limited to frontotemporal dementia and its variants, frontal variant, primary progressive aphasia (semantic dementia and progressive nonfluent aphasia), corticobasal degeneration, supranuclear palsy; epilepsy; NS trauma; NS infections; NS inflammation, including inflammation from autoimmune disorders, including NMDAR encephalitis, and cytopathology from toxins, (including microbial toxins, heavy metals, and pesticides etc.); stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; Fragile X syndrome; Angelman syndrome; hereditary ataxias; neurootologic and eye movement disorders; neurodegenerative diseases of the retina such as glaucoma, diabetic retinopathy, and age-related macular degeneration; Amyotrophic Lateral Sclerosis; tardive dyskinesias; hyperkinetic disorders; attention deficit hyperactivity disorder and attention deficit disorders; Restless Leg Syndrome; Tourette syndrome; schizophrenia; autism spectrum disorders; tuberous sclerosis; Rett syndrome; cerebral palsy; reward system disorders including eating disorders [including anorexia nervosa (AN) and bulimia nervosa (BN); and binge eating disorder (BED), trichotillomania, dermotillomania, nail biting; migraine; fibromyalgia; and peripheral neuropathy of any etiology.Symptoms or manifestations of disorders of the nervous system that can be treated or prevented by neuroplastic substances and drugs include: a decline, deterioration, or abnormality in cognitive abilities including executive function, attention, cognitive speed, memory, language functions ( speaking, comprehension, reading and writing), orientation in space and time, practice, ability to perform actions, ability to recognize faces or objects, concentration, and alertness; abnormal movements including akathisia, bradykinesia, tics, myoclonus, dyskinesias, including dyskinesias related to Huntington's disease, levodopa-induced dyskinesias, and neuroleptic-induced dyskinesias, dystonias, tremors, including essential tremor, and restless leg syndrome; parasomnias, insomnia, disturbed sleep pattern; psychosis; delirium; agitation; headache; motor weakness, spasticity, impaired physical endurance; sensory impairment, including vision impairment and visual field defects, smell, taste, hearing and balance, and dysesthesias; dysautonomia; and ataxia, impaired balance or coordination, ringing in the ears, neuro-otological and eye movement impairments, neurological symptoms of alcohol withdrawal, including delirium, headache, tremors, hallucinations, hypertension ; the treatment of psychiatric disorders as defined by DMS5 and ICD11 that may benefit from modulation of neural plasticity, including Schizophrenia spectrum disorders and other psychiatric disorders, Bipolar and related disorders, depressive disorders, anxiety disorders, obsessive-compulsive disorders and related disorders, trauma- and stress-related disorders, dissociative disorders, somatic symptom disorders and related disorders, eating and eating disorders, elimination disorders, sleep-wake disorders, sexual dysfunction, gender dysphoria, disruptive disorders, impulse control, and behavioral disorders related to substances and addictions, Neurocognitive disorders, Personality disorders, Paraphilic disorders; treatment of systemic inflammatory states and autoimmune disorders; the treatment of aging, senescence and associated deficits, including osteoporosis; treatment of dry eye syndrome; treatment of restless leg syndrome. In any of these methods, the function can be chosen from visual, auditory, sense of balance, olfactory, taste. In any of these methods, the substance may be psilocybin, psilocin, norpsilocin, baeocystin, nor-baeocystin, or a mixture thereof; and / or the substance is a modified release formulation of psilocybin, psilocin, norpsilocin, baeocystin, norbaeocystin, or a mixture thereof. In certain modalities, the drug is a combination of at least two drugs, the first drug is chosen among 5-HT2A agonists, including psilocybin or psilocin or norpsilocin or baeocystin or norbaeocystin at doses of 0.01-24 mg and the second drug is chosen from an open channel low affinity non-competitive NMDAR antagonist, including dextromethorphan, dextromethadone, ketamine and its isomers, memantine, amantadine, noribogaine at doses of 0.01-50 mg; wherein the administration of the combination substance provides synergistic effects and or improved safety over the administration of either substance alone. Also, any of the methods can occur in combination with magnesium and or zinc and or lithium and salts thereof; wherein the administration of the combination substance provides synergistic effects and or improved safety over the administration of either substance alone. The method may include daily oral administration of mushrooms containing psilocybin and / or psilocin and / or baeocystin and / or extracts thereof. In either method, the substance may be coated with an emetic drug to reduce the abuse potential of the substance. And, administration of the substance is performed orally, buccally, sublingually, rectally, vaginally, nasally, via aerosol, trans-dermally, trans crooon / Lznz / q / υιλι mucosal, parenterally (for example, intravenous, intradermal, subcutaneous, and intramuscular), epidurally, intrathecally, intra-auricularly, intraocularly, including implanted reservoir formulations, or topically, including skin or eye creams, lotions, gels and ointments, and eye drops. It is known that fluoride can increase the lipophilicity of a molecule to allow for greater cleavage in membranes and to facilitate hydrophobic interactions with a target receptor. In the case of psychedelics, fluorination of the ring results in a loss of psychedelic effects, while maintaining 5-HT2A affinities, suggesting that activity at this receptor, while necessary, may not be sufficient for psychedelic effects. (Blair JB1, Kurrasch-Orbaugh D, Marona-Lewicka D, Cumbay MG, Watts VJ, Barker EL, Nichols DE. Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines. J Med Chem. 2000 Nov 30;43(24): 4701-10). The effects of neural plasticity and neuroprotective effects may instead be maintained despite the loss of psychedelic effects, and therefore, in light of the present inventors' disclosure, certain fluoro derivatives may be of particular interest for the neuroplastic therapeutic programs of the present inventors, for which, as described above in more detail, the psychedelic / psychotomimetic effects are unwanted side effects rather than therapeutic effects. Novel designed drugs characterized by 5-HT2A affinity and loss of psychedelic effects obtained with ring fluorination may thus be particularly desirable for the therapeutic indications described in this application, and particularly for the condition and diseases that may benefit. of the modulation of NMDARs and / or effects of neural plasticity. Furthermore, if a nitro derivative of a psychedelic drug is to prove itself effective for a specific disease, this therapeutic effect may derive from Snitrosylation of over-reactive NMDARs WITHOUT induced channel closure, as may be the case for nitro-derivatives. memantines (Tomohiro Nakamura and Stuart A. Lipton. Protein S-Nitrosylation as a Therapeutic Target for Neurodegenerative Diseases. Trends in Pharmacological Sciences, January 2016, Vol. 37, No. 1) or could be for another reason altogether (Stamler et al ., U.S. Patent number US5593876A; Inturrisi, CE. NMDA receptors, nitric oxide and opioid tolerance. Regulatory Peptides, 1994, Volume 54, Issue 1), including, as disclosed in this application, due to a subtype differential modulation of the 5-HT receptor or other receptors. Furthermore, although ROS reactive radicals and reactive nitrogen species (RNS) are normal components of cellular metabolism, over-production of these types of radicals leads to the cell's inability to regulate them, leading to redox imbalance and redox imbalance. formation of oxidative stress. A nitro derivative of a psychedelic drug with potential neural plasticity and neuro-protective actions may regulate these reactive radicals and prevent or decrease croaon / Lznz / q / υιλι cell damage by this or other mechanisms. Simply increasing the affinity for 5HT2A receptors is not necessarily therapeutically advantageous for the indications described in this application: LSD is a very potent psychedelic (the effective dose to induce psychedelic effects is measured in micrograms) but may not offer neuroprotection improved over other neuroplastic molecules administered at comparable dosages devoid of psychedelic / psychotomimetic effects; very high potency may instead represent safety concerns, as in the case of LSD. On the other hand, changes in the molecular structure of selected neuroplastics that determine changes in their PK and PD functions may prove to be advantageous for selected diseases and thus the synthesis of fluoro derivatives and nitro derivatives, and deuterated compounds, including some Combinations of these modifications (including deuterated fluoronitro derivatives), among other possible structural modifications, may result in novel potentially effective therapeutic molecules for the indications described in this application. Finally, the present inventors postulate that there is close proximity of 5-HT2A receptors and NMDARs within postsynaptic mega-complexes. This proximity can determine allosteric interactions, therefore the activation of 5-HT2A by certain agonists at this receptor can also be modulated, for example, inhibit (shut down), the NMDAR channel open, and vice versa, NMDAR blockers as well. can interact with 5-HT2A receptors [(in addition, some NMDAR blockers also inhibit the SERT and NET pathway (Codd et al, 1995) and more importantly the NMDAR antagonist dextromethadone exerts affinity for 5-HT-receptors 2A in the nanomolar range (Rickli et al., 2017).] The present inventors are currently testing these interactions in electrophysiological models to determine relationships within NMDAR subtype receptor and 5-HT receptor subtype affinities and affinities. to select other receptors, including dopamine receptors, sigma 1 receptors, histamine receptors of different molecules within both of these classes of drug substances (NMDAR antagonists and 5-HT2A agonists, including novel designer drugs) subtypes 5- HT1A; 5-HT1B; 5-HT1D; 5-HT2A; 5-HT2B; 5-HT2C; 5-HT5; 5-HT6; 5-HT7; GAVE ; D2L; D3; D4; D5; SERT; NET; MOP; PDO; KOP; H1 Sigma 1; NMDAR2A, 2B, 2C, 2D). The present inventors are also testing the affinity of nitro derivatives that can be agonists at 5-HT2A receptors and determining the block of NMDA by interacting with the open channel outer domain, as described above for nitro derivatives. Derivatives of 5-HT2A agonists of particular interest include psilocybin, psilocincarbamate, psilocin, norpsilocin, DMT, DMO, LSD, baeocystin, norbaeocystin, noribogaine derivatives; fluoro (F) derivatives, including fluoro-psilocybin; nitro (NO) derivatives, including nitro-psilocybin; fluoro-nitro derivatives, including fluoro-nitro-psilocybin; modified deuterated 5-HT2A agonist derivatives as above for psilocybin, including deuterated fluoro croaon / Lznz / q / υιλι (F) derivatives, including fluoro-psilocybin, deuterated nitro (NO) derivatives, including nitropsilocybin, and derivatives of deuterated fluoro-nitros, including fluoro-nitro-psilocybin. The same derivatives listed above for psilocybin are described for psilocin, norpsilocin, DMT, DMO, LSD, baeocystin, norbaeocystin, noribogaine, and carbamate derivatives thereof. See also Table 1A. For purposes of this disclosure, the present inventors define prodrugs or pro-drugs as compounds with moieties that can be hydrolyzed in vivo, both chemically and enzymatically, to release the active compound. Examples of prodrugs and their uses are well known in the art (See, for example, Rautio et al. (2018) Nature Reviews Drug Discovery volume 17, pages 559-587). Prodrugs can be prepared in situ during final isolation and purification of the compounds, or by separate reaction of the purified compound with a suitable derivatizing agent. Examples of prodrug moieties include branched or unbranched, substituted and unsubstituted alkyl ester moieties (for example, propionic acid esters), alkenyl esters, dialkylamino alkyl esters (for example, dimethylaminoethyl ester), acylamino alkyl esters (for example, , acetyloxymethyl ester), acyloxy alkyl esters (for example, pivaloyloxymethyl ester), aryl esters (for example, phenyl ester), aryl alkyl esters (for example, benzilester), aryl and arylalkyl esters, amides, alkylamides, dialkyl amides, and hydroxy amides , alkyl carbamates, dialkyl carbamates each optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol , thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate. Preferred prodrug moieties of the invention are N-monosubstituted carbamates of amino acids (eg L-Isoleucyl, L-Leucyl, L-Alanyl, β-Alanyl, L-Valinyl etc.). The invention can include a compound of any formula in Table 1A, salts, and prodrugs thereof. Psilocybin (PSY) is believed to act as a prodrug for the corresponding psilocin (PSI) in vivo (Jacob III, P.; Shulgin, A.T. in NIDA Research Monograph 146 (Hallucinogens, an Update), 2000, Eds. Lin, G.C.; Glennon , R.A., pp. 74). PSY is dephosphorylated by alkaline phosphatase to active PSI. In addition, PSI chemically degrades rapidly in the presence of air, heat, and / or light. This is due to the presence of the free group 4- hydroxy on the tryptamine scaffold, which is susceptible to oxidation On the other hand, PSY is much more stable than PSI due to the presence of a phosphate ester, which protects the 4-OH group from degradation, both chemical and metabolic Thus, the prodrug approach has proven to be a successful tool for exploiting the pharmacological activity of PSI. The invention also relates to new carbamate prodrugs of PSI (4 crooon / Lznz / q / υιλι carbamoyl indoles) and derivatives, also substituted at the 5-, 6-, and / or 7-positions in which the 4-hydroxyl moiety it is reversibly protected as a carbamate ester linked to the N-terminus of a natural amino acid. Lipophilic amino acid carbamate ester prodrugs of phenolic compounds have been shown to strongly enhance bioavailability by increasing absorption 5 after oral administration, reducing metabolism, and leading to sustained release, up to 24 hours, of low concentrations of the compound. active particularly in brain tissue (See, for example, Azzolini et al. (2017) Eur J Pharm Biopharm volume 115, pages 149-158). A sustained release of the active compound at low concentration could represent an advantage for safe pharmacological uses of PSI (and derivatives) by avoiding psychedelic / psychotomimetic effects after PSY (and derivatives) administration while maintaining the ability to promote plasticity both structural and functional in brain tissue. For further clarification, the concept of pro-drug is relative to the effect of the target, for example the agonist action at the 5-HT2A receptor. However, for a different target effect (eg NMDAR modulation) at a different postulated site (eg NMDAR pore channel), as was postulated for drugs classified as 5-HT2A agonists and their derivatives listed in Table 1A, the prodrug for the 5-HT2A receptor may also function as a pore channel blocking drug, as suggested by the present inventors' docking results (see Table IB, below) for the psilocybin and carbamate prodrugs. crooon / 1 znz / q / υιλι croaon / Lznz / q / υιλι CPQQQn / iznz / q / ΥΙΛΙ IBO title gl ae gscc'e: -7.58 NIBO title g ¡de gscore: -7.27 title PSI14 gHae gscc'e: -7.077 title DDL·'' g ¡de gscore: -6.989 title PSI10 gl ae gscc'e: -6.897 title PSI9 g gscore: -7.'63 IBO1 title gl ae gscc'e: -6.861 title |BC7 g ¡de gscore: -6.853 croaon / Lznz / q / υιλι croaon / Lznz / q / υιλι crooon / Lznz / q / υιλι croaon / Lznz / q / υιλι croaon / Lznz / q / υιλι croaon / Lznz / q / υιλι croaon / Lznz / q / υιλι crooon / Lznz / q / υιλι croaon / Lznz / q / υιλι CPQQQn / iznz / q / ΥΙΛΙ The typical effects of psychedelics at moderately high doses [eg, 12-20 mg (0.178-0.254 mg / Kg) of psilocybin result in plasma psilocin Cmax levels of 4.8-12.3 ng / ml. (Hasler F, Bourquin D, Brenneisen R, Bar T, Vollenweider FX. Determination of psilocin and 4-hydroxyindole-3-acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 1997 ;72(3):175-184.doi:10.1016 / s00316865(97)00014-9) include increased intensity and increased lability of affective responses and distortions of perceptual, visual, auditory, and tactile processes. In another study by Hasler et al. 2004 (Hasler F, Grimberg U, Benz MA, HuberT, Vollenweider FX. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology (Berl). 2004;172(2 ): 145-156. doi:10.1007 / s00213-003-1640-6) looking for effects at different doses of psilocybin, the threshold dose of 0.045 mg / kg defined as very low dose (the high dose in this study was close to ten times as much, 0.315 mg / kg) was rated as clearly psychoactive by the majority of study subjects. Mild drowsiness and increased sensitivity and intensification of pre-existing mood states were the most prominent effects at this very low dose of psilocybin. The findings by Hasler et al, 1994 and 2004, teach the opposite of the potential uses of 5-HT2A agonists for non-psychiatric illnesses and symptoms, and also contradict the potential uses of 5-HT2A agonists for use potential for psychiatric illness and symptoms when psychedelic and psychotomimetic effects are contraindicated or not required for therapeutic activity. In addition, the findings of increased intensity and lability of affective responses by Hasler with very low doses and the findings of Polito's study on microdosing cited above teach the opposite of potential neuropsychiatric therapeutic actions, including teaching the opposite of positive effects. in cognitive abilities (nootropic effects) or in the increase of the special senses, including vision. In fact, the production of distortion of visual, auditory and tactile processes teaches the opposite of the use of these substances for the treatment of ophthalmological diseases and of their potential to improve vision in general or to improve other special senses, including loss of vision. hearing and ringing in the ears. Also, for subsets of psychiatric patients, including those suffering from illnesses and symptoms currently under clinical investigation (depression, addiction, post-traumatic stress disorder, anxiety), the current mode of administration of 5-HT agonists and Psilocybin in particular, which includes a single session during which a large dose of psychedelics is administered, may be detrimental rather than therapeutic. According to the present inventors' present disclosure, these psychiatric patients could instead potentially benefit from repeated, non-psychedelic, small doses (dosages, posology and neuroplastic formulations). The potentially effective dose tested in the experimental models of the present inventors (0.01 mg / Kg) corresponds to less than 1 / 4 of the very low dose defined by Hasler (0.045 mg / Kg) (see experimental details below). The psychotomimetic / psychedelic effects of psychedelic substances appear to be primarily but not solely mediated by serotonin receptors and in particular 5-HT2A receptors, based on experimental studies with moderately selective 5-HT2A antagonists (eg, ketanserin, blocking psychedelic effects), selective agonists (for example, lorcaserin, selective for 5-HT2C and devoid of psychedelic effects), and based on the correlation of the relative potency of psychedelic effects with the 5-HT2A affinity of different drugs ( K¡ for LSD, psilocin, DMT: 3.5; 107; 127). In addition to their affinity for 5-HT2A receptors, most psychedelics show moderate to high croaon / Lznz / q / υιλι affinity for many other receptors, including other serotonin receptors but also dopamine receptors and histamine receptors. (Halberstadt AL, Geyer MA. Multiple receptors contribute to behavioral effects of indoleamine hallucinogens. Neuropharmacology. 2011 Sep;61(3):364-81). Although mind-altering effects, including effects on sensory distortion induced by psychedelics appear to correlate with 5-HT2A receptor affinity, actions at other receptors, including 5-HT1, and or dopamine receptors probably contribute. these effects and other factors related to ais PK characteristics are also important (Blair JB, Kurrasch-Orbaugh D, Marona-Lewicka D, Cumbay MG, Watts VJ, Barker EL, Nichols DE. Effect of ring fluorination on the pharmacology of hallucinogenic tryptamines J Med Chem. 2000 Nov 30;43(24):4701-10). Based on the present inventors' novel experimental work detailed below and a thorough review of available data from the literature, the present inventors describe a novel mechanism for 5-HT2A agonist-induced neuroplasticity: the 5-HT2A agonist may be secondary to modulation of the synthesis of NMDAR subunits, an action possibly mediated via the blocking effects of NMDAR via allosteric interactions. This effect can be initiated and maintained by acute downregulation of 5-HT2A receptors, which is the basis for the known acute tolerance that develops from high-dose (psychedelic) administration of 5-HT2A agonists. The chronic downregulation of 5-HT2A receptors determined by chronic dose (multiple doses administered over days or months) may thus underlie neural plasticity effects mediated by NMDAR modulation, which is potentially therapeutic for a multiplicity of conditions. conditions and disorders. The potential neurological, metabolic, and ophthalmic therapeutic effects discussed below may also be determined at least in part by actions at receptors other than 5-HT2A and or mediated by other mechanisms, including as yet undiscovered mechanisms, including those that may result from binding to 5-HT2A receptors, and which may be present, or differentially present, at dosages that do not produce psychotomimetic / psychedelic effects and thus are potentially therapeutic for a multiplicity of diseases and conditions for which psychotomimetic effects and psychedelics are harmful side effects. In addition, other properties may also be important in determining psychotomimetic effects, such as receptor on / off time, thus offering potential parameters for clinical efficacy improvement for newly designed SMSNs with neuroplastic effect but devoid of psychotomimetic effects even at higher dosages, thus widening the therapeutic window for novel non-psychedelic 5-HT2A agonist drugs. croaon / Lznz / q / υιλι Although findings of the potential for modulation of neural plasticity by indolamines and other psychedelics are becoming increasingly understood (Ly et al., 2018), the potential therapeutic value of these substances and drugs beyond psychiatric illness, and beyond the modulation of neural plasticity and the potential for neuroprotective effects that can be achieved without psychedelic / psychotomimetic effects, needs to be explored beyond the current research focus that currently remains centered around the administration of 5-agonists. -HT2A in isolated treatment sessions at doses that cause intense psychedelic / psychotomimetic effects for the treatment of psychiatric illnesses. In summary, the psychedelic experience and its strong psychotomimetic effects are still thought to be integral and necessary for psychiatric therapeutic effects, by the layman, the user as well as for scientific communication. The heavy sociocultural weight carried by these substances and the current scientific vision focused on psychiatric diseases and mainly on psychedelic treatments for depression, are so strong that they can be defined closely as psychedelics or at most psychoplastic (Ly et al., 2018 ), with reference to its ability to induce a potentially therapeutic psychedelic experience, with potentially therapeutic effects limited to the psychiatric field, without acknowledging that therapeutic effects may be present at chronically administered neuroplastic doses, as shown by novel research by the present inventors. , and may be therapeutic outside the psychiatric field for metabolic, ophthalmologic, and neurologic diseases and conditions. Thus, the present inventors describe herein that 5-HT2A agonist drugs devoid of psychedelic effects (for example, psilocybin 0.1-4 mg), have neuroplastic effects, and are potentially therapeutic for a multiplicity of diseases and conditions, which may include but are not limited to psychiatric disorders, as described throughout this application. The importance of administering neuroplastic doses of drugs with effects on neural plasticity repeated over time is instead well recognized for NMDAR antagonists with the potential for the treatment of neurological diseases. The present inventors reviewed the available literature for the open-channel NMDAR blocker dextromethadone in many published studies and published patent applications in light of the present inventors' observations, results, and disclosures: In a single ascending dose study ( SAD) where doses of 5-200 mg were tested, only the lowest tested dose of 5 mg dextromethadone produced a nootropic signal (International Patent Application No. PCT / US2018 / 016159). In this study the MTD was set at 150 mg (nausea and vomiting), so the supposed nootropic dose was 1 / 30 of the MTD. In a multiple ascending dose (MAD) trial where 25, 50, and 75 mg doses were tested over a 14-day period, only the lowest dose (25 mg daily) resulted in a statistically significant increase in plasma BDNF (De Martin et al., 2018). croaon / Lznz / q / υιλι A recent study compared the cognitive effects of psilocybin 10,20,30mg and dextromethorphan 400mg. This study found dose-dependent negative effects of psilocybin on psychomotor performance, working memory, episodic memory, associative learning, and visual perception, which again teaches the opposite of the current description. The effects of the 400 mg dose of dextromethorphan on psychomotor performance, visual perception, and associative learning were in the range of effects of a moderate to high dose (20 to 30 mg / 70 kg) of psilocybin. This was the first study of the dose effects of psilocybin and dextromethorphan on a large battery of neurocognitive assessments. Psilocybin had greater effects than DXM on working memory. DXM had greater effects than all doses of psilocybin on balance, episodic memory, response inhibition, and executive control (Barrett FS, Carbonaro TM, Hurwitz E, Johnson MW, Griffiths RR. Double-blind comparison of the two hallucinogens psilocybin and dextromethorphan: effects on cognition. Psychopharmacology (Berl). 2018 Oct;235(10):2915-2927). Notably, the proven dose of dextromethorphan, 400 mg, is much higher than the dose used in formulations approved for neurological therapeutic effects (the FDA-approved dose of dextromethorphan for the pseudobulbar effect is 20 mg, a much lower dose compared to with the 400 mg used in the previous study, even when accounting for the metabolic block achieved by quinidine). Based on previous observations for the NMDAR open channel blocker dextromethadone (International Patent Application No. PCT / US2018 / 016159; De Martin et al., 2018) and the dose-dependent cognitive effects observed in the Barrett 2018 study for dextromethorphan and psilocybin, the present inventors disclose not only that the effects of 5-HT agonists and NMDAR antagonists are similar in their potential to induce neural plasticity, as seen in in vitro and in vivo studies, but that the clinically advantageous therapeutic actions of these drugs may be present only at low neuroplastic doses and not necessarily at higher doses, and that there is a ceiling to the therapeutic dose and that psychedelic effects may represent the ceiling for therapeutic effects, at least for most disorders and patients who may benefit from nonpsychedelic neuroplastics: when the dose of NMDAR antagonists and the dose of 5-HT2A agonist are high enough to result in psychedelic, dissociative, psychotomimetic, and type symptoms of neurocognitive impairments described by Barrett et al, 2018, the therapeutic effect of these substances for some or all of the indications described here is probably compromised. The same is true for ketamine which at high doses is an anesthetic and at lower doses it is an FDA approved antidepressant (esketamine). However, based on the present inventors' observations and findings, the present inventors disclose that at lower doses devoid of the side effects of croaon / 1 znz / q / υιλι psychedelic experience (at doses of approximately 1 / 10 -1 / 20 of psychedelic doses), drugs in both classes, 5-HT2A agonists and NMDAR channel-opening blockers, exert neuroplastic actions with potential therapeutic effects for a multiplicity of diseases and conditions. The psychedelic experience and psychotomimetic symptoms induced by these drugs, which in the current scientific view are essential for therapeutic actions, particularly for certain psychiatric disorders, may therefore be a side effect that can be avoided by administering a lower dose in a repeat schedule, daily, every other day, every third day, weekly, biweekly, or monthly, or chronic daily schedule for most indications described in this application. For further clarification, neuroplastic effects adequate to exert clinically significant effects for a multiplicity of diseases are induced by doses of 5-HT agonists much lower than the doses in current use by laymen, including traditional tribal users, recreational uses, and therapists and the dose used in ongoing clinical trials for psychiatric disorders, including those at large university centers in the U.S.A. Finally, effects on neural plasticity, and not the psychedelic experience, are the basis for major potential therapeutic actions, including potential therapeutic effects for disorders and conditions of the nervous system, metabolic disorders, ophthalmologic disorders, including effects on the special senses, the effects on aging and including some of the effects on psychiatric disorders for which psychedelic effects may not be necessary and thus represent detrimental side effects. Although the present inventors cannot exclude that for certain patients the psychedelic experience may be therapeutic (clinical trials are ongoing), the present inventors disclose that there is a large group of psychiatric patients who may benefit from neuroplastics (non-psychedelic repeated doses of 5-HT agonists) for whom the psychedelic experience is detrimental and so for these patients a much safer and lower dose of drug may be needed, for example 0.1mg-4mg psilocybin or psilocybin equivalent, and administered in a regular basis (continuous or intermittent) for days or months or chronically, instead of the currently used doses of 8-50 mg administered in a single session. Furthermore, at lower neuroplastic doses, the agonist effect at 5-HT2A receptors is not clinically significant, especially if this effect of 5-HT2A is defined by its ability to induce psychedelic / psychotomimetic effects. As shown in our experiment of Example 3, the neuroplastic effects of these drugs classified as 5-HT2A agonists may be secondary to modulatory actions on NMDAR. The same concept is held for NMDAR antagonists, but for these drugs the concept is already understood by the scientific community and the approved therapeutic dose for croaon / Lznz / q / υιλι dextromethorphan is well below the dose that causes dissociative symptoms and the dose of dextromethadone under clinical investigation does not cause psychotomimetic effects (International Patent Application No. PCT / US2018 / 016159; Relmada.com). Furthermore, the present inventors hypothesize that at least some of the neuroplastic effects may not be induced by direct agonist interaction with 5-HT2A receptors and the subsequent downstream cascade but may be secondary to other mechanisms including downregulation / modulation of 5-HT receptor expression, including 5-HT52A receptors, after exposure to 5-HT agonists and for potential effects on other receptors such as NMDARs and AMPA receptors and receptors DA and histamine and sigma 1 and opioids. Some of the neuroplastic effects, including those potentially therapeutic for a multiplicity of diseases and conditions, may therefore be better achieved by the administration of repeated small doses of drugs devoid of psychedelic / psychotomimetic effects, rather than being administered as a single large dose with effects. psychedelics / psychotomimetics. Ly et al., 2018, have studied the acute in vitro and in vivo effects of large doses of many compounds with 5-HT2A agonist activity (however, Ly et al., 2018, did not specifically study psilocin / psilocybin and did not study the NMDAR antagonists and do not describe the possible actions of drugs classified as 5-HT2A agonists on NMDARs). The studies by Ly et al., 2018 were designed to access the mechanisms underlying the clinical findings of the effects of large doses of select drugs that produce psychedelic and psychotomimetic effects in patients with psychiatric disorders and in particular the effects of these drugs on patients with depression and anxiety. The findings by Ly et al. 2018, support their hypothesis: large doses (doses expected to produce psychedelic and psychotomimetic effects in humans) of psychedelics potentially promote functional neural plasticity in prefrontal cortical neurons and this effect potentially results in the antidepressant and anxiolytic effects seen in patients currently under investigation in phase 2 clinical trials. The present inventors performed a different subset of experiments as detailed below, to test a different hypothesis: chronically administered, low neuroplastic dosages of drugs classified as 5-agonists and modulators. HT2A, exert neuroplastic effects by modulating NMDARs and thus may be potentially therapeutic for diseases and conditions and for the improvement of functions, including vision. Although the current DEA schedule (Schedule I) for 5HT2A agonist drugs may change as to therapeutic indications and range of effects are better defined by ongoing clinical studies for psychiatric uses, abuse concerns , partially driven by sociocultural forces, still make these drugs unattractive croaon / Lznz / q / υιλι for development as pharmaceutical agents (Sellers EM, Romach MK, Leiderman DB. Studies with psychedelic drugs in human volunteers. Neuropharmacology. 2018 Nov; 142:116-134). Currently, investigators of psychedelic drugs for the treatment of psychiatric illnesses have only considered their use at high (psychedelic) doses in a single session in supervised settings. This requirement for patient and / or supervised administration may reduce the potential for abuse as the drug is administered directly in a supervised setting, usually by a therapist, with reduced risk for diversion. The relative potential for safety and low addiction of these substances has been underestimated in recent scientific publications (Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances Act. Neuropharmacology. 2018 Nov;142:143-166.), however, the potential for abuse of pharmaceutical 5-HT2A agonists is realistic and the potential for harmful effects when these drugs are taken recreationally, while generally not serious, is limited. well-documented, with nearly 6,000 cases with psilocybin-containing mushrooms reported in U.S. poison centers. From January 1, 2000 to December 31, 2016 (Leonard JB, Anderson B, Klein-Schwartz W. Does getting high hurt? Characterization of cases of LSD and psilocybincontaining mushroom exposures to national poison centers between 2000 and 2016. J Psychopharmacol 2018 Dec;32(12): 1286-1294). Therefore, the potential for abuse of 5-HT agonists with neuroplastic effects raises safety concerns, especially if these drugs with neuroplastic actions are intended for long-term, out-patient therapy in relatively unsupervised settings: recreational users, seeking from the psychedelic experience, they could potentially abuse the drug by self-administering many tablets at once, more than the prescribed non-psychedelic / psychotomimetic dose. To minimize the abuse potential of these substances the present inventors describe formulation strategies that introduce anti-abuse aspects that have the potential to reduce their abuse potential, even when administered in an out-patient setting. The present inventors therefore describe the combination of a neuroplastic with an emetic drug, including an emetic incorporated into a capsule or tablet coating, including emetic drugs that act on the CTZ in the medulla and or gastrointestinal irritants. The present inventors describe an abuse-arresting formulation comprising the combination of a neuroplastic with the potential to cause psychedelic effects when abused (for example, ingestion of 10 times the prescribed neuroplastic dose can potentially induce psychedelic effects) with an emetic drug. low-dose: the emetic drug dose is ineffective when the drug is taken as prescribed (for example, one or two tablets at a time) but the emetic dose becomes effective if a subject attempts to abuse the drug and ingests a larger crooon / Lznz / q / υιλι doses (multiple tablets, eg over three tablets at a time) with the intent to induce psychedelic effects (eg 5-10 tablets at a time could potentially induce psychedelic effects). Of interest, even without the induction of emesis, which may occur only when higher doses are ingested (for example, 10 times or more than the prescribed dose), less severe but still discouraging effects of nausea may occur when abuse is it is limited to 3-5 times the prescribed dose and these discouraging effects may be enough to limit future abuse (even the weak psychedelic experience sought by a potential drug abuser could be greatly impoverished by the accompanying nausea). Along the same lines the present inventors also describe other drug forms and methods discouraging abuse that can be combined with MR 5-HT neuroplastics, including when combined with emetic drugs, including when formulated as long-acting and / or slow release: (1) incorporation of an excipient that gels when mixed with water, alcohol, or other common solvents; (2) incorporation of a physical barrier that resists crushing, dissolving, melting, or chemical extraction; (3) formulation of very strong tablets that are extremely hard to break or alter; (4) chemically engineered prodrugs that require enzymatic cleavage in vivo to produce a pharmacological effect (for example, an amide bond formed between the drug molecule and a single amino acid such as lysine or a small oligopeptide (up to 15 amino acids), an ester bond formed between a hydroxyl group on the drug and a carboxylic group on the carrier, complexation with an ion exchange resin, complexation with a metal cation, complexation with a fatty acid); (5) incorporation of another aversive ingredient, in addition to or as an alternative to the emetic drug: (For example, a purgative agent [niacin], a diuretic, a laxative, or irritant [capsaicin]; nasal irritants, emetic agents, bittering agents , and effervescent agents; and / or (6) co-formulation with a sequestered antagonist or aversion agent that is released upon product alteration. Modified Release (MR) Formulations Although some patients / diseases and conditions may benefit from IR psilocybin at non-psychedelic / psychotomimetic doses (eg, 2-4 mg or less), subsets of patients or select diseases and conditions may require a slightly higher dose of psilocybin or other 5H-2a agonist (eg, baeocystin MR) for optimal neuroplastic action. However, for these patients the psychedelic / psychotomimetic effects could be detrimental. Indeed, large subsets of patients, particularly those who could benefit most from neuroplastics (such as patients with neurodevelopmental and neurodegenerative disorders, and elderly patients, and all patients with some form of cognitive impairment, including minimal cognitive impairment , and many patients with crooon / Lznz / q / υιλι psychiatric disorders as defined by DSM5), are probably more susceptible to experiencing harmful psychedelic and psychotomimetic side effects if doses greater than 2-4 mg of psilocybin IR are administered. This inter-individual variability in psychedelic / psychotomimetic experimentation is well documented. Inter-subject pharmacological PK variability factors and non-pharmacological variability factors both play an important role in inter-subject susceptibility to psychedelic / psychotomimetic side effects of neuroplastics. Therefore, although the psychedelic / psychotomimetic effects of 5HT2A agonists are directly related to the doses administered [Studerus E, Kometer M, Hasler F, Vollenweider FX. Acute, subacute, and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol. 2011 Nov;25(ll):1434-52]; Studerus E, Gamma A, Kometer M, Vollenweider FX. Prediction of Psilocybin Response in Healthy Volunteers. PLOS ONE. 2012;7], and plasma levels, which also correlate with 5H2A receptor occupancy [Madsen, M.K; Burmester, D; Stenbaek, D.S. Psilocybin occupancy of brain serotonin 2A receptors correlates with psilocin levels and subjective experience: a (11C) Cimbi-36 PET study in humans. European Neuropsychopharmacology, 2019, Volume 29], some patients will be unable to tolerate even the very low (eg, less than 1 mg psilocybin or psilocybin equivalent) potentially effective dose of psilocybin IR dose without incurring cognitive side effects, including psychedelic / psychotomimetic side effects. Appropriately designed MR formulations of 5-HT2A agonists, capable of targeting specific PK parameters (Cmax, AUC, Tmax) and PD effects (receptor occupancy and psychedelic / psychotomimetic effects or lack thereof) as described detailed later, it can be effective for these patients. In addition to dose, and individual PK and psychiatric variables, the difference in pharmacokinetic parameters caused by the route of psilocybin administration also plays an important role in psychedelic / psychotomimetic effects: the high Cmax (12.9+- 5.6 ng / mL) and short Tmax (1.9+-1 min) of IV psilocybin 1 mg compared to oral psilocybin 10-20 mg (similar Cmax: 8.2+-2.8 ng / mL; longer Tmax: 105+-37 min) produced similar psychedelic effects despite the much lower AUC for IV administered drug (240+-55 vs. 1963+-659) (Hasler F, Bourquin D, Brenneisen R, Bar T, Vollenweider FX. Determination of psilocin and 4-hydroxyindole3- Acetic acid in plasma by HPLC-ECD and pharmacokinetic profiles of oral and intravenous psilocybin in man. Pharm Acta Helv. 1997 Jun;72(3): 175-84). Probably Cmax and Tmax are also increased (Cmax) and shortened (Tmax), similar to IV administration, when the drug is inhaled intranasally, rather than taken orally. Considering the importance of dose and route, PK parameters and other variables related to subsets of patients and / or diseases and crooon / Lznz / q / υιλι selected conditions, a modified-release formulation (oral or transdermal) can optimize PK parameters ( and PD effects) by neuroplastic actions without cognitive side effects, rather than by psychedelic effects, by allowing administration of higher daily doses without the side effects of psychedelic / psychotomimetic effects, by maintaining lower Cmax and longer Tmax and higher or equal AUC compared to agonists of 5-HT2A IR agonists. As discussed above, the patients who can benefit from most neuroplastic drugs, such as patients with neurodevelopmental and neurodegenerative disorders and elderly patients, and patients with even minimal cognitive impairments, are also those with the lowest tolerance and with increased risk from psychedelic and psychotomimetic effects. The present inventors therefore describe the use of modified-release formulations of 5-HT2A agonists (for example, psilocybin MR and baeocystin MR) that optimize PK parameters compared to the same 5-HT2A IR dose: lower Cmax, slower Tmax, increased Tl / 2, and comparable or larger AUC. This modified-release formulation will allow administration of higher dosages of psilocybin than could be tolerated with the IR formulation, thus avoiding psychedelic / psychotomimetic side effects, allowing for example doses of up to 32 mg of psilocybin, a dose that in the IR formulation will elicit psychedelic / psychotomimetic effects in most patients, and also allowing for very low doses, eg 0.5mg psilocybin, which in select clinical settings (eg dementia) or for highly sensitive individual patients, may be tolerated alone in an MR formulation and not in IR formulations. The paper by Madsen et al., cited above, correlates psychedelic / psychotomimetic symptoms with plasma psilocin levels and 5-HT2A receptor occupancy. In this study a 3 mg oral dose of IR psilocybin (the lowest dose tested in the study) determined psychedelic / psychotomimetic effects, psilocin Cmax of 2.4 ng / ml and 42.9% 5-HT2A receptor occupancy. The intensity of psychedelic / psychotomimetic symptoms was mild compared to the highest doses tested resulting in more intense psychedelic / psychotomimetic effects, higher Cmax (up to 19.3), and higher receptor occupancy (up to 72.4%). Note, the subject with the highest receptor occupancy (72.4%) was not the subject with the highest plasma psilocin levels, suggesting additional potential inter-individual variables, other than Cmax, in determining receptor occupancy. (eg, CNS drug penetration, receptor variables, including affinity status of receptors). Additionally, especially as technology progresses and testing costs decrease, assessment of receptor occupancy may help predict tolerance of neuroplastic doses of 5-HT2A agonists without psychedelic / psychotomimetic side effects [for example, Receptor occupancy equal to or less than 40% (or less than 50% or less than 30%) can predict good tolerance to the tested neuroplastic dose. Thus, croaon / Lznz / q / υιλι a 5-HT2A receptor occupancy test can help the physician to prescribe the appropriate neuroplastic dose for an individual patient. Finally, due to the effects of PK and / or PD, including receptor modulation and receptor occupancy, the combination of 5-HT2A agonists and NMDA antagonists, including the combination of psilocybin and dextromethadone, may offer synergistic advantages while decreases the potential for psychedelic / psychotomimetic and other side effects, as discussed throughout this application. The different subtypes of NMDARs are known to change through life expectancy: NMDAR2Bs are more prevalent at a younger stage of development and later in development they are replaced by NMDAR2As. NMDAR2B appear to have a longer activation time and thus this receptor subtype has been associated with increased long-term potentiation (LTP) and some phases of life (young age) are characterized by facilitated learning, for example, language learning. This naturally occurring NMDAR subtype switch (2B —> 2A) could potentially be physiologically modulated by actions on 5-HT2A receptors by endogenous agonists (eg, DMT). Low dose 5-HT2A agonists could exert enhanced neuroplastic modulatory actions, as seen in the present inventors' in vitro experiments in ARPE-19 cells. Although the present inventors cannot exclude that psychedelic symptoms may be therapeutic in select diseases and for select psychiatric symptoms or for select patients, as hypothesized by some investigators (clinical trials to answer this question are ongoing), the current view It is challenged by laymen and the scientific community that psychedelic / psychotomimetic effects are always necessary for the potential therapeutic activity of 5-HT2A agonists, by the observations, experimental results and disclosures of the present inventors. The present inventors therefore disclose that neuroplastics, as defined above, and comprising 5-HT agonists, including 5-HT agonists with potential modulatory activity on NMDARs and their subtypes, potentially exert their therapeutic neuroplastic effects at doses that they do not produce psychedelic / psychotomimetic / dissociative effects and do not produce negative neurocognitive side effects and may actually result in nootropic effects, especially if neurocognitive testing is performed after the drug has had time to exert its CNS-modulating plasticity actions ( chronic dosing). For this purpose, the present inventors are verifying, both in vitro and in vivo, the changes in the expression of the NMDAR receptor and the expression of the 5-HT receptor, including its subtypes and its subunits, induced by neuroplastic drugs. Based on the present inventors' experimental results (described in croaon / Lznz / q / υιλι examples, following) the present inventors disclose that selected 5-HT agonists, including those with activity at the 5-HT2A receptor, including psilocybin, can modulate endogenous receptors, including 5-HT2A receptors and / or NMDARs, in a manner similar to endogenous neurotransmitters, including DMT. The direct actions of 5HT2A agonists on 5-HT2A receptors, and the direct or indirect actions on the NMDARs described in this application, and or the actions on neuroplastic-induced serotonin receptor downregulation of exogenous 5-HT2A , potentially modulate the expression of NMDARs (they increase in mRNA and subunit proteins shown in the experiments of the present inventors) and in particular, drugs in this pharmacological class can modulate the expression of NMDARs, and specifically the transcription and synthesis of subunit proteins that make up the NMDAR NR1-2A, NR1-2B, NR1-2C and NR1-2D subtypes, including NR1-2A-2B and other triheteromeric combinations. Subtype 2B NMDARs are known to be most prominent during early development and are thought to play an important role in the learning abilities of the developing brain. During development, the NMDAR 2B subtype is progressively replaced by the 2A subtype which eventually predominates in the adult brain. Thus, it is conceivable that neuroplastics by modulating subtypes of NMDARs could potentially recreate the level of neural plasticity seen during early development and thus favor and promote new neural circuitry and / or neural repair and thus be potentially therapeutic for a multiplicity of diseases and conditions. , especially diseases and conditions that affect sensory pathways and memory and learning (learning is not limited to memory and cognition but also determines motor skills, social skills and emotional functions). Finally, neuroplastics in the 5-HT2A agonist class may improve the outcomes of rehabilitation programs, including neurorehabilitation programs, including those focused on cognition, language, vision, and including rehabilitation programs for substance use disorders. substances, including rehabilitation focused on physical therapy. Improvement in rehabilitation outcome is achieved by increasing and modulating neural plasticity and neural circuitry involved in learning. Furthermore, while there may be subsets of patients among those suffering from psychiatric disorders who may benefit from the psychedelic experience (as there are psychiatric patients who benefit from ECT), based on the in vitro and in vivo and clinical results of the The present inventors, the present inventors disclose that other patients, including subsets of psychiatric patients, will similarly benefit from treatment with ongoing treatment with non-psychedelic neuroplastics administered at low doses, including intermittent dosing and including in modified-release formulations. crooon / 1 znz / q / υιλι Treatment with neuroplastics at non-psychedelic doses probably has additional benefits when associated with appropriate psychotherapy and neurorehabilitation programmes. Finally the fact that ketamine, a neuroplastic in the NMDAR antagonist drug class is FDA-approved for depression at doses that are psychedelic / psychotomimetic or doses that are at the edge of the psychedelic / psychotomimetic window (dissociative symptoms), and that psilocybin is in clinical trials at psychedelic doses, suggests that there may be a subset of patients who benefit from higher psychedelic / psychotomimetic doses, or alternatively, it may mean that those patients might also benefit (or alternatively, might actually benefit even more). ) of much lower doses, non-psychedelics, and long-term formulations of the same drugs, when tested in appropriately designed clinical trials. Furthermore, both magnesium and zinc are modulators on the NMDAR. Magnesium is an NMDAR blocker and thus for the reasons and results described above the combination of magnesium with 5-HT2A agonists may be synergistic. Zinc is a modulator of NMDAR, and thus, for the reasons and results described above, the combination of zinc with or without magnesium with 5-HT2A agonists may be synergistic. Magnesium supplementation has been shown to have the potential to improve hypertension, insulin sensitivity, hyperglycemia, diabetes mellitus, left ventricular hypertrophy, and dyslipidemia; Additionally, magnesium can treat certain types of seizures (for example, those that occur as part of eclampsia) and can be used for arrhythmias such as torsades de pointes. [Houston M. The role of magnesium in hypertension and cardiovascular disease. J Clin Hypertens (Greenwich). 2011 Nov;13(ll):843-7]; [Rosanoff A. Magnesium and hypertension. Clin Calcium. 2005 Feb;15(2):255-60], The combination of 5-HT2A agonists with magnesium and / or zinc and salts thereof may be potentially synergistic for the treatment of diseases and conditions that may benefit from the modulation of the neural plasticity and may result in drugs not only with improved efficacy but also with improved safety. In the case of blister packs for intermittent dosing, magnesium and / or zinc could be substituted for inactive doses on non-therapy days (eg, every three days). Chronic administration of NMDA causes mitochondrial dysfunction in rats [Kim, H.K. et al., Mitochondrial dysfunction and lipid peroxidation in rat frontal cortex by chronic NMDA administration can be partially prevented by lithium treatment. J Psychiatrist Res. 2016 May;76:59-65]. Thus, lithium combined with NMDAR antagonists may offer greater safety over NMDAR antagonists alone. According to Leslie et al., 1993, the combination of 5-HT2A agonists with lithium may enhance the potential antidepressant actions of 5-HT2A agonists (Leslie RA, Moorman JM, Grahame-Smith DG. Lithium enhances 5-HT2A receptor -mediated c-fos croaon / Lznz / q / υιλι expression in rat cerebral cortex. Neuroreport. 1993 Dec 13;5(3):241-4). Taken together with the present inventors' new evidence for the potential neuroplastic actions of non-psychedelic doses of the 5-HT2A agonist, the lithium-induced increase in c-fos expression seen by Leslie et al. may also be suggestive of a synergy potential not only for antidepressant effects but also for neuro-modulatory effects (neuroplastic effects). Based on the observations, findings, and descriptions of the present inventors, and planned and ongoing in vitro, in vivo, non-psychotomimetic, low-dose clinical studies of known 5-HT2A agonists and novel drugs listed in Table 1A (SMSNs), defined herein as neuroplastic, administered repeatedly over days, months, or chronically, can activate serotonin and other receptors, including 5-HT2A receptors, in different cell lines, including retinal pigment cells (thus also influencing the activity of and photoreceptor vitality), other retinal cells, and specialized olfactory, auditory, balance cells, and neurons and astrocytes (including astrocyte-like cells in the retina, eg, Muller cells), and specific neuronal populations, including retinal ganglion cells and other neurons involved in visual pathways, including cortical neurons, including hippocampal neurons, and which exert trophic functions, and modulate and generate new and / or stronger synoptic activity and new connections, thereby improving the function of the special senses, improving memory and learning, in subjects and patients with sensory impairments from a multitude of diseases and conditions and improving neurological functions, including visual function, other sensory functions, and cognitive functions, in subjects with neurological impairments from a multitude of diseases and conditions, including diseases and neurological, psychiatric, metabolic deficits of aging, including senescence. In particular, the trophic and protective effects on retinal pigment epithelial cells and astrocytes may be of particular importance for their role in narrowing the retinal blood barrier and the BBB and thus in supplying nutrients, neurotransmitters, and other crucial molecules to neurons of the brain. CNS and receptors that are part of visual pathways and other sensory pathways, including photoreceptors, and for their scavenging and other important roles in neural plasticity. Due to their neural plasticity effects, including trophic effects on cells, and due to anti-inflammatory effects, the effects of 5-HT2A agonist substances and SMSNs may not only survive elimination from the body, but under some circumstances , the positive effects may be more apparent or only apparent after the substance has been substantially removed. This may be particularly relevant for some visual and cognitive improvements, especially when the dose of the NMDAR antagonist and / or 5-HT2A agonist drugs and / or their combination is sufficient to elicit CNS symptoms such as psychotomimetic or psychedelic symptoms. croaon / Lznz / q / υιλι The work on inflammation and serotonin by Banganz (Baganz,N.L.& Blakely,R.D. A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem. Neurosci. 4, 48-63 (2013) and Arreóla ​​( Arreóla, R. et al. Immunomodulatory effects mediated by serotonin J Immunol Res. 2015, 354957 (2015) and work by Flanagan and Nichols (Flanagan TW, Nichols CD. Psychedelics as anti-inflammatory agents. Int Rev Psychiatry. 2018 Aug 13:1 -13), are all in accordance with the present inventors' clinical observations and experimental results and with the present inventors' findings and descriptions: the agonist actions of psychedelics on serotonin receptors, primarily 5-HT2A receptors but also actions at other receptors, including non-serotonin receptors, can shorten inflammation, including TNF-α-mediated inflammation.Based on the present inventors' experimental results, these anti-inflammatory effects potentially have a role in improving the neurological functions, including vision, or may prevent neurological deficits, including neurological and ophthalmological deficits associated with aging and cellular senescence, including visual deficits in CNS diseases where inflammation potentially plays a role, such as neurodegenerative and neurodevelopmental diseases , including diseases where inflammation of the visual pathways (anywhere from retinal pigment cells to cortical structures) is involved. A modulation of systemic indicators of inflammation may also ameliorate psychiatric symptoms and syndromes, including depression, which have been associated with systemic inflammation. The results of the recent study by Madsen et al. [Madsen, M.K; Burmester, D; Stenbaek, D.S. Psilocybin occupancy of brain serotonin 2A receptors correlates with psilocin levels and subjective experience: a (11C) Cimbi-36 PET study in humans. European Neuropsychopharmacology, 2019, Volume 29] suggest that the psychedelic effects of psilocybin are dose-correlated and thus a lower dose will not produce psychotomimetic / psychedelic effects, in accordance with the observations and descriptions of the present inventors. In addition, also according to the clinical observations, experimental results and descriptions for the safety indications and therapeutic potential of the present inventors, not only the psychotomimetic effects, but also other side effects of psychedelic substances, such as headache, fatigue and increases in blood pressure are dose dependent (MW Johnson, Sewell AR. Griffiths RR. Psilocybin dose-dependently causes delayed, transient headaches in healthy volunteers Drug and Alcohol Dependence, 2011, Volume 123, Issue 1; Studerus E, Kometer M , Hasler F, Vollenweider FX. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol. 2011 Nov;25(ll):1434-52), confirming that relatively minor doses of psychedelics are probably not only safe but also well tolerated and devoid of psychotomimetic and other side effects. On the other hand, the croaon / 1 znz / q / υιλι anti-inflammatory actions appear to be active at very low doses (Psychedelics as medicines; an emerging new paradigm), again supporting novel observations in patients by the present inventors and the present inventors' novel experimental data and thus supporting the development of psychedelics as medicines for neurological and ophthalmological and metabolic indications, and not only for prichiatric indications, as described throughout this application, at non-psychedelic doses and with formulations not psychedelic. In the 2011 study by Studerus et al., (Studerus E, Kometer M, Hasler F, Vollenweider FX. Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies. J Psychopharmacol. 2011 Nov;25(ll): 1434-52) the present inventors noted an improvement in restless leg symptoms in 2 patients treated with psilocybin (see Table 2 in Studerus et al., 2011). The present inventors also noted a similar improvement in one of the present inventors' patients (CF). This observation, although limited to three patients, indicating that three patients possibly suffering from restless legs syndrome improved after treatment with the 5-HT agonists, taken together with the present inventors' new data on the antagonistic actions of 5-HT. NMDAR of selected 5-HT agonists and the effects of these drugs on the glutamatergic pathway and excitotoxicity, suggests a possible therapeutic activity for 5-HT2A agonists in restless leg syndrome (RLS). A hyper-glutamatergic state has been postulated as a mechanism for RLS. Clinical observations, experimental results and disclosures by the present inventors teach that relatively low doses of 5-HT agonist substances administered repeatedly over days or months or even chronically, continuously or intermittently have the potential to be safe and well tolerated and devoid of clinically significant side effects, including psychotomimetic and other typical psychedelic effects, and cognitive side effects. Thus, neuroplastics and SMSNs, when dosed appropriately, may be safe and effective for the management of diseases and conditions listed throughout this application and for improving vision and cognition, a multiplicity of neuropsychiatric diseases and conditions, and metabolic disorders. including metabolic syndrome. The psychedelic effects of 5-HT2A agonists to date have been so inherent in the potential for therapeutic benefits (centered around psychiatric illnesses) of 5-HT2A agonist drugs and not as side effects. In the present inventors' disclosure psychotomimetic effects are side effects caused by overdose, while neuroplasticity and amelioration of diseases and conditions seen with appropriate lower dosages and formulations are therapeutic effects. Psychotomimetic effects can be minimized or avoided by using non-psychedelic dosages and formulations of these croaon / Lznz / q / υιλι substances administered repeatedly over time and by applying structural molecular modifications to known 5-HT2A agonists (see Table 1A), which result in SMSNs with better PK and PD parameters. Based on the present inventors' descriptions, observations, and experimental results, doses of IR psilocybin equal to or less than 4 mg (or doses equivalent to the psychedelic potency of other 5-HT2A agonists and NMDAR antagonists) may be sufficient to modulate neuroplasticity that could potentially treat the multiplicity of disorders and conditions listed in this application. In fact, according to the observations and results of the present inventors, neuroplastic effects are potentially more prominent when lower concentrations are maintained over time rather than when a higher concentration is administered in single sessions [see also BDNF results cited for the phase 1 study of dextromethadone where the increase in BDNF reached statistical significance only in the 25 mg group and not in the 50 or 75 mg groups, (De Martin et al., 2018)]. However, for select diseases and / or subgroups or individuals of select patients, a higher dose of a neuroplastic drug may be required to exert the appropriate modulation of neural plasticity that will ameliorate a particular disease or condition: in such a patient administration of a release preparation Modified or long-acting or slow-release 5-HT2A agonist may be appropriate as detailed below. Psychedelic effects are known to be linked to dose, plasma levels and receptor occupancy: higher doses correspond to higher blood levels and higher receptor occupancy and more prominent psychedelic symptoms [Madsen, M.K; Burmester, D; Stenbaek, D.S. Psilocybin occupancy of brain serotonin 2A receptors correlates with psilocin levels and subjective experience: a (11C) Cimb¡-36 PET study in humans. European Neuropsychopharmacology, 2019, Volume 29]; (Brown RT, Nicholas CR, Cozzi NV, Gassman MC, Cooper KM, Muller D, Thomas CD, Hetzel SJ, Henriquez KM, Ribaudo AS, Hutson PR. Pharmacokinetics of Escalating Doses of Oral Psilocybin in Healthy Adults. Clin Pharmacokinet. 2017 Dec ;56(12): 1543-1554). The neuroplastic effects are instead potentially driven by additional and consequential mechanisms and not just by direct drug binding to 5-HT2A receptors. Neuroplastic effects, as shown by the present inventors' in vitro work, in vivo work, and clinical observations, may actually be enhanced by lower doses / concentrations compared to higher doses (for example, psychedelic / psychotomimetic dosages). and thus present at non-psychedelic / psychotomimetic dosages. The modified-release, long-acting, and / or slow-release formulation of a neuroplastic drug will allow the administration of a relatively higher amount of drug while still avoiding the psychedelic and / or psychotomimetic side effects caused by a spike in drug blood levels (the effects psychedelics caused by high Cmax and short Tmax). The present inventors crooon / Lznz / q / υιλι therefore also describe long-acting and / or slow-release modified-release neuroplastic formulations, including long-acting and / or slow-release oral or transdermal formulations of psilocybin and or baeocystin at doses up to 30 mg per 24 hours (or a dose of other 5-HT2A agonists and NMDAR antagonists with equivalent psychedelic / psychotomimetic potency, and thus also devoid of these effects). The long-acting / slow-release modified-release formulation is designed to maintain plasma levels of psilocin below the 4-6 ng / mL window that elicits psychedelic and / or psychotomimetic effects for psilocin (or a plasma level of equivalent psychedelic potency other 5-HT2A agonists and / or NMDAR antagonists) so they will not determine plasma levels sufficient for psychedelic effects. Finally, the long-acting and / or slow-release modified-release preparation may allow administration of larger doses of 5-HT agonists that may be indicated for select diseases and conditions among those listed above, and / or may be indicated for select subjects, for example, subjects who may be more sensitive to the psychedelic and / or psychotomimetic effects of these drugs than average, thus allowing effective treatment by widening the therapeutic window for these drugs. The same reasoning behind the therapeutic role of psychedelics for ophthalmologic disorders can be applied to other pathologic conditions of other sensory organs and pathways such as hearing / balance deficits - otologic disorders and olfactory / smell detection and or gustatory / taste disorders. and disorders of tactile sensations, including certain sexual disorders, particularly those associated with senescence. These substances and drugs could potentially ameliorate or safely prevent or delay sensory loss (vision, hearing, balance, smell, taste, and somatosensory) associated with senescence. The present inventors further disclose that the neural plasticity effects of these drugs may involve extra neuronal cells, such as retinal pigment cells, and astrocytes and neurons outside of the prefrontal cortex and thus result in effects and a potentially therapeutic effect in a multitude. of neurological and ophthalmological syndromes (beyond psychiatric disorders), not only by promoting neurite outgrowth but also via neuroprotective mechanisms, including protection from excitotoxicity, and anti-inflammatory mechanisms, as detailed in clinical observations, experiments, and descriptions of the present inventors. In particular the present inventors' disclosures reveal that these effects of 5HT agonists are not limited to neurons but also involve retinal pigment epithelial cells, and potentially other cells such as liver and pancreatic cells as shown and noted in the novel experiments of the present inventors (see Examples 1 to 3). Furthermore, the present inventors underestimate the potential role of astrocytes, since these cells have been found to express 5-HT2A receptors [Xu TI, Pandey SC. Cellular localization of crooon / Lznz / q / υιλι serotonin(2A) (5-HT2A) receptors in the rat brain. Brain Res Bull. 2000 Apr;51(6):499-505], in supporting the present inventors' disclosure: as mentioned above, the effects of psychedelics on astrocytes and retinal pigment cells may be of particular importance because of their role in narrowing the retinal blood and BBB barrier and thus in supplying nutrients, neurotransmitters, and other crucial molecules to CNS neurons and photoreceptors that are part of visual pathways, and for its purifying and other important roles in neural plasticity . Current scientific understanding of psychedelic effects on cognitive function teaches the opposite of the use of psychedelics to improve cognitive function (Bayne T, Carter O. Dimensions of consciousness and the psychedelic State. Neurosci Conscious. 2018;2018(l) ): The findings are grouped into three broad categories (sensory perception, cognitive function, and unity experiences) and demonstrate that although certain aspects of consciousness are enhanced or heightened in the psychedelic state, many of the functional abilities that are associated with conscience are seriously compromised. Finally, since the mechanisms of neural plasticity modulation by psychedelics can be driven by experience, the present inventors describe the importance of timing the administration of these substances and drugs (known 5-HT2A agonists and the detailed modified novel molecules in Table 1A) with specific activities (including activities of daily living and specific mental activities and specific neuro-rehabilitation programmes, including visual rehabilitation programmes). This coupling of drug and activity may offer additional advantages for the use of these drugs as neurological and ophthalmological treatments, including neurological and ophthalmological rehabilitation treatments. Timing of neuroplastic treatment to achieve relatively high levels during specific activities and progressive reduction of plasma and tissue drug levels in the evening hours, which can potentially result in consolidation of neural plasticity during physiological sleep (with very low or ineffective drug levels), may thus be of importance. This reasoning could point towards the administration of the 5-HT2A serotonin agonist substance in such a way as to achieve higher serum levels during the day and during specific neuro-rehabilitation sessions and lower levels during sleep. In the subjects reported by the present inventors the administration of psilocybin-containing substances was timed with intense visual testing and the present inventors postulate that this programming may have had a potentially beneficial effect on the positive results on day 5, after substantially elimination. of all psychedelic substance (48 hours after the last dose). Based on immunohistochemical and morphological results suggesting crooon / Lznz / q / υιλι effects of neural plasticity for low-dose and repeatedly administered 5-HT2A agonists, the present inventors disclose that substances acting on 5-HT2A receptors and other CNS receptors and SMSNs may not only be useful for the treatment of psychiatric illnesses and symptoms, including depression in all its forms, anxiety in all its forms, PTSD, adjective behaviors, and drug addiction, but can potentially prevent these illnesses and symptoms when administered in anticipation of life stressors or during stress or shortly after stressful events, before the development of illness or psychiatric symptoms. By promoting neural plasticity and by other mechanisms, such as modulating 5-HT2A receptor pathways, NMDARs, SERT and NET, and BDNF, 5-HT2A agonists and SMSNs may increase resilience to developing psychiatric illnesses and symptoms. when administered during periods of life laden with mental stressors or when a mental stressor is anticipated and thus may be useful for the prevention of psychiatric illnesses and symptoms, including those triggered by mental stress from a multiplicity of causes including social stress, bereavement, illness, personal loss, marital and family-related stress, financial stress, war, natural and man-made disasters, etc. This description is supported by the experimental results by Brachman for ketamine, (Brachman RA, McGowan JC, Perusini JN, et al. Ketamine as a Prophylactic Against Stress-Induced Depressive-like Behavior. Biol Psychiatry. 2015;79(9): 776-786): Ketamine is an NMDAR antagonist that potentially shares neuroplasticity effects with select 5-HT2A agonists. In the US, the prevalence of metabolic syndrome increased from 1988 to 2012 for every sociodemographic group; by 2012, more than one-third of all American adults meet the definition and criteria for metabolic syndrome agreed upon jointly by many international organizations. (Moore JX, Chaudhary N, Akinyemiju T. Metabolic Syndrome Prevalence by Race / Ethnicity and Sex in the United States, National Health and Nutrition Examination Survey, 1988-2012. Prev Chronic Dis 2017; 14:160287. DOI: http: / / dx.doi.org / 10.5888 / pcdl4.160287) Metabolic syndrome is associated with cardiovascular disease, obesity, arthritis, NAFL, NASH, MDD, schizophrenia, dementia, and cancer. The present inventors' results suggest that neuroplastic 5-HT2A agonists, eg, chronic low-dose psilocybin, as stand-alone therapy or with the low-dose NMDAR antagonist, may ameliorate one or more features of the metabolic syndrome. Based on the experimental findings of the present inventors, 5-HT2A neuroplastic drugs point to strong therapeutic potential for the treatment of metabolic syndrome, not only as an appetite suppressant and anti-obesity drug but as a potentially lifestyle-modifying treatment. disease with actions and influences at the molecular level in hepatocytes (decrease in steatosis), Langherhans cells (decrease in glycemic peak), and in immune cells (decrease in inflammatory markers). croaon / Lznz / q / υιλι Metabolic disorders that can be treated or prevented by neuroplastic substances and drugs include: metabolic syndrome, obesity, hyperglycemia, type 2 diabetes mellitus, high blood pressure, coronary artery disease including myocardial infarction and unstable angina, liver disease Non-alcoholic fatty acids (NAFLD) and non-alcoholic steatohepatitis (NASH), hypogonadism, testosterone deficiency, hypothalamic-pituitary axis disorders, and BDNF deficiency, including WAGR syndrome, llp deletion, llp inversion, and Prader syndromes -Willi, Smith-Magenis, and ROHHAD. In 2015, a total of 1.02 million people became blind, and approximately 3.22 million people in the United States had visual impairment (best corrected visual acuity in the better seeing eye). By 2050, the numbers of these conditions are projected to double to approximately 2.01 million blind, 6.95 million visually impaired (Varma Rl, Vajaranant TS2, Burkemper B3, Wu S3, Torres M3, Hsu C3, Choudhury F3 , McKean-Cowdin R4.Visual Impairment and Blindness in Adults in the United States: Demographic and Geographic Variations From 2015 to 2050. JAMA Ophthalmol. 2016 Jul l;134(7):802-9). Currently available medications are inadequate for the treatment of ocular diseases and conditions associated with visual impairment; there has been little innovation in this area in recent decades. The need for better treatments remains, especially for visual impairment associated with retinal diseases, including those associated with aging. Sight or vision (adjective form: visual / optical) is the ability of the eye(s) to focus and detect images of visible light on photoreceptors in the retina of each eye that generate electrical nerve impulses for colors Variable , tints, and brightness. There are two types of photoreceptors: rods and cones, the rods are very sensitive to light but do not distinguish colors. The cones distinguish colors but are less sensitive to light intensity. Stereopsis, depth perception using both eyes, is generally a cognitive (i.e., postsensory) function of the brain's visual cortex where patterns and objects in images are recognized and interpreted based on previously learned information (visual memory). ). People who are blind from degradation or damage to the visual cortex, but still have functional eyes, are actually capable of some level of vision and reaction to visual stimuli but not conscious perception; this is known as blindsight. Blindsighted people typically do not know they are reacting to visual sources, instead only unconsciously adapting their behavior to the stimulus. Neuroplastics may have a role in improving vision affected by disease and injury at all levels of the visual pathways from the retina to the cortical croaon / Lznz / q / υιλι areas and for all levels of vision loss, including patients with partial or complete cortical blindness where they can prevent retinal pathology and restore some vision or at least maintain blindsight. The multifactorial decline in vision secondary to aging can also be slowed or ameliorated by neuroplastic substances. The improvement in vision of neuroplastics includes improvements in visual acuity, contrast sensitivity, color vision, visual fields, and stereopsis. Neurodegenerative, neurodevelopmental and inflammatory diseases of the retina such as glaucoma, diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, optic neuritis, and LHON and refractive disorders are among the diseases that could potentially be ameliorated by neuroplastic substances, including SMSNs. Eye diseases and their symptoms and signs that may respond to neuroplastic drugs and SMSNs include all of the disorders listed above. In neurodegenerative diseases of the retina such as glaucoma, diabetic retinopathy, and age-related macular degeneration, during metabolic stress, glutamate is released, initiating the dysfunction and death of neurons that contain ionotropic NMDA receptors, such as retinal ganglion cells and a specific type of amacrine cells. The main causes of cell death after the activation of NMDA receptors are the entry of calcium into cells, the generation of free radicals linked to the formation of advanced glycation end products (AGEs) and / or advanced lipoxidation end products ( ALEs), as well as defects in the mitochondrial respiratory chain. Macular edema represents the final stage of multiple pathophysiological pathways in a multitude of vascular, inflammatory, metabolic, and other diseases; novel treatments, such as neuroprotective agents, such as nerve growth factors and NMDA antagonists, can inhibit neuronal cell death in the retina (Wolfensberger TJ. Macular Edema - Rationale for Therapy. Dev OphthalmoL 2017;58: 74-86). Similar damage to nerve cells induced by NMDA can occur in glaucoma and optic neuritis. Meanwhile, an NMDA antagonist has been found to potentially benefit glaucoma in an experimental study (Celiker H et al., Neuroprotective Effects of Memantine in the Retina of Glaucomatous Rats: An Electron Microscope Study.J Ophthalmic Vis Res. 2016 Apr -Jun;ll(2):174-82); the authors concluded that when initiated early in the glaucomatous procedure, memantine may help preserve retinal ultrastructure and thus prevent neuronal injury in experimentally induced glaucoma. Memantine was also found to be effective in reducing retinal nerve fiber layer (RNFL) thinning in patients with optic neuritis (Esfahani MR et al., Memantine for axonal loss of optic neuritis. Graefes Arch Clin Exp OphthalmoL 2012 Jun ;250(6):863-9), although vision did not improve. An observation previously decontextualized by Honygllo et al. on the croaon / Lznz / q / υιλι distribution of psilocin in the human body after ingestion of psilocybin mushrooms, has now added weight to the present inventors' description of potential therapeutic ophthalmic activity. . After ingestion of psilocybin mushrooms, psilocin was quantified in peripheral and cardiac blood as 60 and 67 ng / mL, respectively, and in urine (2,230 ng / mL), bile (3,102 ng / mL), and vitreous humor. (57ng / mL). (Honyiglo, E Franchi A; Cartiser: Unpredictable Behavior Under the Influence of Magic Mushrooms: A Case Report and Review of the Literature. Journal of Forensic Sciences, 12 / 2018). The comparable blood and vitreous levels of psilocin seen in this report, taken together with the present inventors' novel clinical observations and experimental results, suggest that following systemic uptake of 5-HT agonists, the retina may be exposed. to psilocin at levels comparable to the levels reached by the systemic circulation. These relatively high levels in the vitreous are potentially suitable for exerting a biological effect on retinal pigment cells (homologous to the ARPE-19 cells used in the present inventors' experiments, see Example 3) and other retinal cells and so on. modulate and enhance important connections and cellular activities within visual pathways, starting from the retina. This finding supports the clinical observations of the present inventors and confirms the experimental findings and descriptions of the present inventors: with the vitreous concentration of psilocin comparable to the concentration seen in blood it is possible that the visual effects of psilocin observed in clinical observations of the present inventors (see Example 1) could also be secondary to retinal exposure from local vitreous diffusion and not only from exposure via the blood retinal barrier or exposure to the BBB by more central NS structures. The long-lasting positive effects on vision seen in our subjects may therefore be secondary to modulation of neural plasticity via different mechanisms, including damping of inflammation anywhere along the pathways of the nervous system, including the retina and visual pathways, including cells made up of retinal pigment cells within the retina and up to cortical areas. Substances that prevent excito-cytotoxic events (excitotoxicity) are considered potentially neuroprotective. Experimental studies show that several drugs reduce or prevent the death of nutrient-deficient retinal neurons. These agents generally block NMDA receptors to prevent glutamate action and arrest the subsequent pathophysiological cycle that results in cell death (Schmidt KG et al., Neurodegenerative diseases of the retina and potential for protection and recovery. Curr Neuropharmacol. 2008 Jun ;6(2): 164-78.). Glutamate-induced optic atrophy has also been found to be associated with alterations in BDNF expression (Ito Y et al., Degeneratlve alterations in the visual pathway after NMDA-induced retinal damage in mice. Brain Res. 2008 May 30;1212 :89-101). Excitotoxic lesion has been postulated as a concurrent pathogenic factor in croaon / 1 znz / q / υιλι Leber's hereditary optic neuropathy (Howell N. Leber hereditary optic neuropathy: respiratory chain dysfunction and degeneration of the optic nerve. 1988 Vis Res 38: 1495-1504. Room G. Antioxidants Partially Restore Glutamate Transport Defect in Leber Hereditary Optic Neuropathy Cybrids. Journal of Neuroscience Research 2008 86:3331-3337). Alterations in glutamate metabolism have been described in different models of retinitis pigmentosa; glutamate-mediated excitotoxic mechanisms were found to contribute to rod photoreceptor death in the mouse model of retinal degeneration (Delyfer MN et al., Evidence for glutamate-mediated excitotoxic mechanisms during photoreceptor degeneration in the rdl mouse retina. Mol Vis 2005 Sep 1;11:688-96). Applicants' novel findings about the modulatory effects of 5-HT2A agonists on NMDARs open up new perspective for their potential uses to prevent excitotoxic neural damage. Psilocybin at neuroplastic dosages shown to be devoid of psychotomimetic effects and to potentially improve visual parameters in human subjects (see Example 1) can potentially treat and or prevent the worsening of many neurological and ophthalmological conditions where alteration of neuronal plasticity or modulation of neural plasticity may play a role and to treat and prevent the worsening of conditions, including diseases where BDNF regulates neuronal plasticity, including diseases of the retina, optic nerve, and optic pathways, whether administered systemically, topically via eye drops, the eyes, and / or intra-ocularly, including intra-vitreous depot formulations. The inventors discovered that the sclerotia of the psilocybe atlantis (magic truffle) improves visual parameters. 5-HT2A agonists stimulate neuroplasticity via the BDNF and mToR pathways (Ly et al., 2018). The effects of BDNF on nerve cells of the eye, including retinal ganglion cells, may prevent or treat neurodegenerative and inflammatory diseases of the retina and eye. Currently available medications are inadequate for the treatment of nervous system disorders, their symptoms, and / or their manifestations; there has been little innovation in this area in recent decades. The need for better treatments remains. Neurological diseases and their symptoms and signs that may respond to neuroplastic drugs and SMSNs include: Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, including mild cognitive impairment associated with aging and chronic disease and its treatment, including chemotherapy, immunotherapy and radiation therapy, Parkinson's disease and related Parkinsonian disorders including but not limited to Parkinson's dementia; disorders associated with the accumulation of amyloid beta protein (including but not limited to cerebrovascular amyloid angiopathy, posterior cortical atrophy); disorders associated with accumulation or disruption of croaon / Lznz / q / υιλι tau protein and its metabolites including but not limited to frontotemporal dementia and its variants, frontal variant, primary progressive aphasia (semantic dementia and progressive nonfluent aphasia), corticobasal degeneration, paralysis supranuclear; epilepsy; NS trauma; NS infections; NS inflammation, including inflammation from autoimmune disorders, including NMDAR encephalitis, and cytopathology from toxins, (including microbial toxins, heavy metals, and pesticides etc.); stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; Fragile X syndrome; Angelman syndrome; hereditary ataxias; neurootologic and eye movement disorders; neurodegenerative diseases of the retina such as glaucoma, diabetic retinopathy, and age-related macular degeneration; Amyotrophic Lateral Sclerosis; tardive dyskinesias; hyperkinetic disorders; attention deficit hyperactivity disorder and attention deficit disorders; Restless Leg Syndrome; Tourette syndrome; schizophrenia; autism spectrum disorders; tuberous sclerosis; Rett syndrome; cerebral palsy; reward system disorders including eating disorders [including anorexia nervosa (AN) and bulimia nervosa (BN); and binge eating disorder (BED), trichotillomania, dermotillomania, nail biting; migraine; fibromyalgia; and peripheral neuropathy of any etiology. The symptom or manifestation of disorders of the nervous system that can be treated or prevented by neuroplastic substances and drugs include: a decline, deterioration, or abnormality in cognitive abilities including executive function, attention, cognitive speed, memory, language functions ( speaking, comprehension, reading and writing), orientation in space and time, practice, ability to perform actions, ability to recognize faces or objects, concentration, and alertness; abnormal movements including akathisia, bradykinesia, tics, myoclonus, dyskinesias, including dyskinesias related to Huntington's disease, levodopa-induced dyskinesias, and neuroleptic-induced dyskinesias, dystonias, tremors, including essential tremor, and restless leg syndrome; parasomnias, insomnia, disturbed sleep pattern; psychosis; delirium; agitation; headache; motor weakness, spasticity, impaired physical endurance; sensory impairment, including vision impairment and visual field defects, smell, taste, hearing and balance, and dysesthesias; dysautonomia; and ataxia, impaired balance or coordination, ringing in the ears, neuro-otological and eye movement impairments, neurological symptoms of alcohol withdrawal, including delirium, headache, tremors, hallucinations, hypertension. Psychiatric disorders and symptoms that can be improved by neuroplastics include those listed in the DSM5 and ICD11, and also include disorders such as Schizophrenia spectrum and other psychotic disorders, Bipolar and related disorders, Depressive disorders, Anxiety disorders, Obsessive- Compulsive and Related Disorders, Trauma and Stressor Related Disorders, Dissociative Disorders, Somatic Symptoms and Croaon / Lznz / q / υιλι Related Disorders, Eating and Eating Disorders, Elimination Disorders, Sleep-Wake Disorders, Sexual Dysfunctions, Dysphoria Disorder Gender, Disruptive, Impulse Control, and Behavioral, Substance and Adjective Related Disorders, Neurocognitive Disorders, Personality Disorders, Paraphilic Disorders. Aging-related disorders and deficits that can be treated or prevented by neuroplastic substances and drugs include: disorders associated with physiological or accelerated aging (including aging accelerated by noxious agents, including medical treatments, including cancer treatments and their symptoms and manifestations are chosen from: cognitive impairments, sarcopenia, osteoporosis, sexual dysfunction, skin aging, hair loss or graying, impaired physical stamina, sensory impairment, including impairment of hearing, balance, smell, taste, and / or vision; fatigue. Hearing Listening or audition is the sense of sound perception. Mechanoreceptors in the inner ear change movement - vibration - into electrical nerve pulses. Since sound is vibration, propagation through a medium, the detection of these vibrations, which is the sense of hearing, is a mechanical sense because these vibrations are mechanically conducted from the eardrum through a series of tiny bones. to hair-like fibers in the inner ear, which detect mechanical motion of the fibers within a range of about 20 to 20,000 hertz, with substantial inter-individual variation. Hearing at high frequencies decreases with increasing age. The inability to hear is called deafness or hearing impairment. Sound can also be detected as vibrations conducted through the body by touch. Neuroplastics may have a role in improving hearing affected by diseases and their treatments and injury at all levels of the auditory pathways from inner ear hair cells to cortical areas. Hearing decline secondary to aging can also be slowed or ameliorated by neuroplastics. Neuroplastics for the improvement of hearing and balance or to alleviate ringing in the ears could be administered topically in the form of ear drops, via iontophoresis to increase penetration into the inner ear, via trans-tympanic injection, including as a reservoir form of the inner ear, or they could be administered systemically. taste and flavor Taste or tasting refers to the ability to detect the flavor of substances such as food, certain minerals, and poisons, etc. The sense of taste is often confused with the sense of flavor, which is a combination of taste and smell perception. The flavor depends on the smell, texture, and temperature as well as taste. Humans receive tastes through sensory organs called taste receptors, or gustatory croaon / Lznz / q / υιλι calculi, concentrated on the upper surface of the tongue. There are five basic tastes: sweet, sour, bitter, salty, and umami. Other tastes such as calcium and free fatty acids may also be basic tastes but have yet to receive wide acceptance. The inability to taste is called ageusia. Neuroplastics may have a role in ameliorating deficits in taste and flavor perception affected by disease, disease treatment, and other injuries at all levels of taste pathways from gustatory calculi to cortical areas. The decline in taste perception secondary to aging may also be slowed or ameliorated by neuroplastics. Smell Smell or smell is a chemical sense, like taste. Unlike taste, there are hundreds of olfactory receptors (388 according to one source), each binding to a particular molecular feature. Odor molecules possess a variety of characteristics and thus excite specific receptors more or less strongly. This combination of excitatory signals from different receptors forms what the present inventors perceive as the odor of the molecule. In the brain, smell is processed by the olfactory system. Olfactory receptor neurons in the nose differ from most other neurons in that they die and regenerate on a regular basis. The inability to smell is called anosmia. Some neurons in the nose are specialized to detect pheromones. Loss of odor is a prodrome for neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Neuroplastics may have a role in ameliorating olfactory deficits affected by diseases, their treatments, and injuries at any and all levels of the olfactory pathways, from olfactory receptors to cortical areas. The decline in the perception of smell secondary to aging may also be slowed or ameliorated by neuroplastics. Prevention of anosmia or amelioration of hyposmia by neuroplastic drugs, in addition to improving the quality of life of patients, may be therapeutic for select neurological diseases and conditions, including neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Neuroplastics for the enhancement of the sense of smell could be administered topically in the form of intranasal sprays, aerosols, via iontophoresis to increase penetration, including as an intranasal depot form, or they could be administered systemically. Touch Touch or somatosensation or mechanoreception is a perception that results from the activation of neural receptors, generally in the skin including hair follicles, but also crooon / 1 znz / q / υιλι in the tongue, throat, cornea, and mucosa. A variety of pressure receptors respond to variations in pressure (steady, differential, sustained, etc.). The sense of touch for irritation caused by insect bites or allergies involves special irritation-specific neurons in the skin and spine. The loss or impairment of the ability to feel anything touched is called tactile anesthesia. Paresthesia is a tingling, stinging, or numb sensation of the skin that can result from nerve damage and can be permanent or temporary. Neuroplastics may have a role in ameliorating deficits in the sense of touch affected by disease, medical treatment, and injury at all levels of the somatosensory pathways of neural receptors in the skin including hair follicles, tongue, throat, cornea, and mucosa. to cortical areas. The decline in touch perception secondary to aging may also be slowed or ameliorated by neuroplastics. Balance and acceleration, vestibular system The sense of balance, equilibrioception, or vestibular is the sense that allows an organism to feel the movement, direction, and acceleration of the body, and to achieve and maintain equilibrium and balance of posture. The organ of equilibrioception is the vestibular labyrinth system found in the inner ear. In technical terms, this organ is responsible for two senses of angular momentum acceleration and linear acceleration (which also detects the force of gravity), but together they are known as equilibrioception. The vestibular nerve conducts information from sensory receptors in three blebs that detect fluid movement in three semicircular canals caused by three-dimensional rotation of the head. The vestibular nerve also carries information from the utricle and saccule, which contain hair-like sensory receptors that bend under the weight of otoliths (small calcium carbonate crystals) that provide the inertia needed to detect head rotation. , the linear acceleration, and the direction of the gravitational force. Neuroplastics may have a role in ameliorating balance deficits affected by disease and injury at all levels of the somatosensory pathways from neural receptors in the inner ear to cortical areas. The decline in the sense of balance secondary to aging may also be slowed or ameliorated by neuroplastics. proprioception Proprioception, the kinesthetic sense, provides the parietal cortex of the brain with information about the movement and relative positions of body parts. Neuroplastics may have a role in ameliorating deficits in proprioception affected by disease, treatment, and injury at all levels of the somatosensory pathways from receptors to cortical areas. The decline in the sense of proprioception secondary to aging may also be slowed or ameliorated by neuroplastics. crooon / Lznz / q / υιλι sexual arousal v sexual function Sexual stimulation is any stimulus (including bodily contact) that leads to, increases, and maintains sexual desire, and can lead to orgasm. Unlike the general sense of touch, sexual arousal is tied strongly to hormonal activity and chemical activations in the body. Although sexual desire can arise without physical stimulation, reaching an orgasm normally requires physical sexual stimulation, stimulation of the Krause-Finger corpuscles found in the erogenous zones of the body. Neuroplastics may have a role in ameliorating sexual dysfunction affected by disease and injury at all levels of sexual stimulus pathways, from neural receptors in the skin including hair follicles, tongue, throat, and mucosa to cortical areas. . Decline in sexual function and bladder control secondary to aging or cancer treatments, including radiation therapy and chemotherapy, may also be slowed or ameliorated by neuroplastics. Additionally, by enhancing and or restoring the senses of smell, vision, hearing, and touch, neuroplastics may also increase libido and sexual function affected by disease and aging. Perception of! time Chronoception refers to how the passage of time is perceived and experienced. Although the sense of time is not associated with a specific sensory system, the work of psychologists and neuroscientists indicates that human brains have a system that governs the perception of time, composed of a highly distributed system involving the cerebral cortex, the cerebellum and the basal ganglia. One particular component, the suprachiasmatic nucleus, is responsible for the circadian (or daily) rhythm, while other cell groupings appear to be capable of maintaining a shorter (ultradian) interval time. One or more dopaminergic pathways in the central nervous system appear to have a strong modulating influence on mental timing, particularly interval scheduling. Psychedelics are known for their potential to profoundly affect one's sense of time. When this sense is disrupted by CNS disease or injury, including ocular disorder, neuroplastics may play a role in restoring physiologic timing. Impairment in timing secondary to aging may also be slowed or ameliorated by neuroplastics. sense of agency The sense of agency refers to the subjective feeling of having chosen a particular action. Some neurological diseases or injuries can lead to a loss of this sense, causing a person to feel like a machine or even leading to hallucinations of being croaon / Lznz / q / υιλι controlled from some external source. The opposite extreme also occurs, with some people experiencing anything in their environment as if they had decided it would happen. When this sense is disrupted by CNS disease or injury, neuroplastics may play a role in restoring this sense. The deterioration of the sense of agency secondary to aging may also be slowed or ameliorated by neuroplastics. Familiarity Recognition memory is sometimes divided into two functions by neuroscientists: familiarity and recollection. A strong sense of familiarity can occur without any recollection, for example in cases of deja vu. The temporal lobe, particularly the perirhinal cortex, responds differently to stimuli that feel new than to things that feel familiar. Firing rates in the perirhinal cortex are connected to the sense of familiarity in humans and other mammals. When this sense is disrupted by CNS disease or injury, and / or eye disease or injury, neuroplastics may play a role in restoring this sense. The deterioration of the sense of familiarity secondary to aging may also be slowed or ameliorated by neuroplastics. Additional literature support for the experimental results described in this application: According to recent research, these two classes of compounds, NMDAR antagonists (De Martin et al, 2018; Fogaca et al, 2019) and 5-HT2A agonists (Ly et al, 2018) share the ability to promote neural plasticity. , to induce trophic actions and may have anti-inflammatory actions and some of these effects may be mediated via BDNF modulation but other mechanisms may potentially play a role. Selected molecules from both classes can thus offer neural protection and cellular protection that can be therapeutic for a multiplicity of clinical disorders. Furthermore, due to the distinct and potentially synergistic mechanisms of actions, respectively to NMDAR and 5-HT2A receptors, and the potential interactions between these two classes of receptors described throughout this application, including allosteric interactions, and reciprocal induction (synthesis of proteins) and modulation (allosteric or intra-channel blocking actions) of receptors, including induction of select protein subunits selective for certain receptor subtypes, these two classes of drugs, NMDAR antagonists and 5-HT2A agonists can have the potential to act synergistically, ie their effects may be additive and advantageous for selected patients and / or diseases. Furthermore, when given together these drugs may be safer than either drug given alone. For example, their co-administration may allow even lower doses to be effective, compared to treatment with a single agent from each class administered alone, for the crooon / Lznz / q / υιλι treatment of certain diseases and conditions. In addition, the neuroplasticity modulatory effects of some of the NMDA channel blockers such as ketamine, dextromethadone, and dextromethorphan may be mediated via the 5-HT receptors for which these drugs have affinities [inhibition of NET and SERT or agonist actions in 5-HT receptors [Kapur S, Seeman P. NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D(2) and serotonin 5-HT(2) receptors - implications for models of schizophrenia. Mol Psychiatry. 2002;7(8):837-44; Codd et al., Serotonin and Norepinephrine activity of centrally acting analgesics: Structural determinants and role in antinociception. IPET 1995; 274(3)1263-1269); Rickli et al., 2017]. Both serotonin agonists and NMDAR antagonists potentially determine neural plasticity effects possibly by modulating BDNF (Ly et al., 2018 and De Martin et al., 2018; Fogaca et al. 2019). Although the present inventors describe a potential synergy between these two distinct classes of drugs, drugs in both classes and select drugs within each of the two classes may potentially have different target clinical indications. The study by Catlow et al., 2013 (Catlow B, Song S, Paredes DA, Kirstein CL, SanchezRamos J) Effects of psilocybin on hippocampal neurogenesis and extinction of trace fear conditioning. Exp Brain Res. 2013 Aug;228(4):481-91) demonstrated that psilocybin reduced hippocampal neurogenesis at high doses although they noted that there was an opposite trend towards an increase in hippocampal neurogenesis at lower doses. This observation gives further support to the present inventors' findings and disclosures, underestimating the importance of dosing when directed toward neural modulatory effects and in particular pointing toward the potential therapeutic effects of lower doses of chronically administered 5-HT2A agonists for the modulation of plasticity, neurogenesis and neuroprotection, as demonstrated by the experiments of the present inventors (particularly Example 3). The 2018 study by Ly et al, (Ly C, Greb AC, Cameron LP, et al. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018;23(l 1):3170-3182) confirms the potential of psychedelics to promote neural plasticity and suggests a mechanism based on the activation of 5-HT2A receptors through mechanisms dependent on BDNF, TrkB and mToRCl. This paper focuses on the potential neuronal plasticity effects of psychedelics on a particular neuronal population (prefrontal neurons) known to be affected in depression and other psychiatric syndromes (PTSD, anxiety, addiction), administered acutely (24 hours) at high concentration, and thus suggests the hypothesis of a better understanding of the potential uses and effects of large doses of psychedelics in the treatment of depression. This study supports the currently investigated single large dose therapeutic approach (psychedelic experience), combined with psychotherapy / counseling, for the uses of the crooon / Lznz / q / υιλι 5-HT2A agonists for the treatment of depression and other symptoms and psychiatric syndromes (addiction, anxiety, PTSD). The present inventors' studies support instead the safety and efficacy hypothesis of chronically, continuously or intermittently administered doses of neuroplastics. EXAMPLES crooon / Lznz / q / υιλι EXAMPLE 1 The following clinical observations were performed in the Netherlands on subjects who self-administered Psilocybe atlantis sclerotium (magictruffles.com). Psilocybe atlantis is a species that contains psilocybin, psilocin, baeocystin, and norbaeocystin (Guzmán G, Hanlin RT, White C. Another new blueing species of Psilocybe from Georgia, U.S.A. Mycotaxon 2003; 86: 179183). To appreciate, the sale and use of sclerotia from psychedelic mushrooms is legal in the Netherlands and the producer of the particular brand and species of sclerotia self-administered by the subjects described indicates taking 15 grams for a psychedelic dose [the amount taken by the first subject, CF, (1.5 grams) was 1 / 10 of the suggested psychedelic dose and the amount taken by the other two subjects, GG and PM, (3 grams) was 1 / 5 of the suggested psychedelic dose]. The present inventors describe CF, an 85-year-old person with a history of mild myopia (-2 diopters, RE and LE) corrected at the time of cataract surgery (age 82) with intraocular lens insertion, who reported improvement in vision (improved vision at a distance, specifically better detection of objects at a distance) after occasional low doses (non-psychotomy) of psilocybe mushroom. Upon the patient's request, after an interval of at least three months without taking mushrooms, drugs or other substances, including prescription drugs, vitamins and supplements, the present inventors performed a visual test and psychometric test (reference value day -0) and on day 3, 2 hours after oral intake (acute effects) of 1.5 grams of psilocybe atlantis sclerotia daily for three days (day-3), and on day 4, 24 hours after the last dose of psilocybe atlantis sclerotia (day 4). Visual Acuity Test, Subject CF:____________________________________________ RE: from 10 / 10 day-0 reference value to 12 / 10 on day-3 and day-4 follow-up________________ LE: from 10 / 10 day-0 reference value to 12 / 10 on day-3 and day-4 follow-up__________________ OU (both eyes): from 10 / 10 day-0 baseline to 12 / 10 on day-3 and day-4 follow-up Ishihara Color Test:__________________________________________________________ RE (right eye): pre-treatment reference value 2 errors; day-3 and post-treatment follow-up day-4, 1 error______________________________________________________________________ OS (left eye): pre-treatment reference value 2 errors; day-3 and post-treatment follow-up day-4, 1 error_____________________________________________________________________ (both eyes): pre-treatment baseline 2 errors; day-3 and post-treatment follow-up day-4, OR errors______________________________________________________________________ MMMSE:_______________________________________________________ 0 / 30, no change, day 0, acute day-3 (2 hours after the first dose) and day-4 follow-up, except for an improved geometric pattern in the follow-up test 24 hours after the last dose of cpooon treatment / lznz / q / υιλι These results suggest persistent (up to 24 hours) visual improvement after repeated (daily for 3 days) dosing of very low doses of psilocybin-containing sclerotia (Psilocybe atlantis sclerotia / 1.5 grams daily for 3 days). The present inventors describe two subjects below. The first subject, GG, is a healthy 56-year-old male. The second subject, PM, is a healthy 57-year-old male with moderate myopia since childhood (-9 diopters), well corrected with contact lenses. No subject has taken drugs, including prescription drugs, food supplements, or vitamin supplements for at least three months prior to baseline evaluation. Visual parameters before (day-O, reference value) and after (day-4, 24 hours after taking the third and last dose) taking 3 grams of Psilocybe atlantis sclerotia / day for 3 days. Spatial Contrast sensitivity was measured by randomized Snellen letters of decreasing contrast according to a logarithmic scale of 0.15 for a constant visual acuity of 0.3. Subject 1 (GG):__________________________________________________________________________ RE : 3.2% 3 / 7* day-0 to 3.2% day-4__________________________________________________________ LE : 3.2% day-0 to 1.1% 6 / 7* day-4__________________________________________________________ OL) (both eyes): 1.1% day-0 to 0.8% 6 / 7 day-4___________________________________________________ Subject 2 (PM):__________________________________________________________ RE: 3.2% 2 / 7* day-0 to 3.2% day-4____________________________________________________________ LE: 4.5% 2 / 7* day-0 to 3.2% day-4________________________________________________________ OU (both eyes ): 3.2% 4 / 7* day-0 to 3.2% day-4__________________________________________ *Number of letters correctly identified among those shown in the corresponding letter row composed of seven letters Visual Acuity Test:_______________ Subject 1 (GG):________________________ RE: 10 / 12 day-0 to 10 / 14 day-4_____________ LE: 10 / 14 day-0 to 10 / 16 day-4_____________ OU (both eyes): 10 / 14 day-0 to 10 / 16 day-4 Subject 2 (PM):___________________ RE: 10 / 10 day-0 to 12 / 10 day-4_____________ LE: 9 / 10 day-0 to 10 / 10 day-4________________ OU (both eyes): 10 / 10 day-0 to 12 / 10 day-4 The present inventors administered the Farnsworth-Munsell Color Hue Vision Test 100 and generated the TES values. The TES is an automated generated value, which calculates the number of bricks placed incorrectly and scales the value for consistent analysis. Average TES scores range from thirty to forty on 5 serial tests; while scores exceeding seventy may point to a marker for color blindness. Lower scores are intended to point to significantly increased color vision accuracy, as the TES score is directly correlated to the number of incorrectly identified bricks, https: / / www.colormunki.com / game / huetest_kiosk Subject 1 (GG):__________________________________________________________ OU (both eyes): 70 days-0 to 16 days-4______________________________________________ Subject 2 (PM):__________________________________________________________ OU (both eyes): 73 days-0 to 40 days-4______________________________________________ To obtain a measure of the global performance of visual performances, the present 10 inventors evaluated the Visual Field Test by means of the Humphrey 30-2 computerized perimetry program which offers a widely accepted, standardized static measurement of light perception. on a background of consistent reproducible illumination, and determined the classic indicators given by the system, Visual field index (in %), defect Mean (in dB): Subject 1 (GG): day-0 day-4 Visual Field Index (VFI): RE: 97% LE: 100% RE: 98% LE: 100% Mean Defect (MD) RE: - 1.78 LE: -0.33 RE: +0.41 LE: +0.04 Subject 2 (PM): day-0 day-4 Visual Field Index (VFI): RE: 99% LE: 93% RE: 100% LE: 99% Default Mean (MD) RE: -1.4 LE: -3.61 RE: -0.16 LE: -0.14 15 Since the highest concentration of photoreceptors is concentrated in the macular area, the Central Visual Field test (macular and peri-macular area) by means of the Humphrey 10-2 computerized perimetry program was evaluated considering the Medium defect (in dB): Subject 1 (GG): day-0 day-4 Mean Defect (MD) RE: -0.50 LE: +0.45 RE: +0.72 LE: +1.19 Subject 2 (PM): day-0 day-4 Mean Defect (MD) RE: -0.95 LE: -0.50 RE: -0.16 LE: -0.14 The sensitivity (in dB) of the fixation point, normally corresponding to the location of the most acute visual performance, was also tested on the Humphrey perimeter (data in dB): crooon / Lznz / q / υιλι Subject 1 (GG): day-0 day-4 Fixation Sensitivity RE: 39 dB LE: 38 dB RE: 39 dB LE: 42 dB Subject 2 (PM): day-0 day-4 Fixation Sensitivity RE: 35dB LE: 36dB RE: 37dB LE: 41dB Pupilometry (scotopic, mesopic, and photonic) was performed in both subjects on day-3, 2 hours post-dose: Subject 1 (GG):___________________________________________________ RE: Scotopic 4.41 days-0 to 5.38 days-3_________________________________________ Mesopic 3.45 day-0 to 4.45 day-3________________________________________________ Photopic 3.26 days-0 to 3.50 days-3_______________________________________________________ Dynamics: + 2.86 day-0 to + 3.37 day-3__________________________________________ LE: Scotopic 4.30 days-0 to 5.00 days-3_________________________________________ Mesopic 3.27 day-0 to 4.49 day-3________________________________________________ Photopic 2.67 days-0 to 3.44 days-3___________________________________________________________ Dynamics: + 2.88 day-0 to +3.30 day-3___________________________________________ Subject 2 (PM):______________________________________________________________ RE: Scotopic 6.09 days-0 to 6.54 days-3_________________________________________ Mesopic 4.60 day-0 to 4.46 day-3________________________________________________ Photopic 3.60 days-0 to 3.65 days-3___________________________________________________________ Dynamics: + 3.37 days-0 to 3.90 days-3___________________________________________ LE: Scotopic 5.94 days-0 to 5.99 days-3___________________________________________ Mesopic 4.72 day-0 to 4.26 day-3________________________________________________ Photopic 3.98 days-0 to 3.45 days-3___________________________________________________________ Dynamics: +4.08 day-0 to +3.83 day-3 The present inventors performed baseline (day 0) and post-dose on day-1 and day-4 of the 5-dimensional Altered State of Consciousness Rating Scale. The results are below in the Summary of Results. Summary of Results: Compared to the reference value, day-0, on day 10 4, 24 hours after the last three-day dose of daily administration of 3 grams of Psilocybe atlantis sclerotia, the present inventors detected an improvement on measures of contrast sensitivity, visual acuity, and color vision compared to baseline day-0 in both test subjects. Visual field indicators also indicated improvement in both subjects. A slight increase in mydriatic tone was noted in both subjects on day-3, 2 hours 15 post-dose, compared to baseline day-0 (pupilometry). The 5-dimensional Altered State of Consciousness Rating Scale in both subjects showed a normal state of consciousness in all areas tested at all times tested (day-0, day-1, day-4), confirming the absence of effects. psychedelics / psychotomimetics, both acutely (day-1, 2 hours post-dose) and, as expected, 24 hours after the last of three daily doses. The above results suggest that repeated low (non-psychedelic / non-psychotomimetic) doses of Psilocybe atlantis sclerotia, resulting in non-psychedelic low plasma levels of psilocybin, psilocin, baeocystin, potentially determine sustained clinically significant effects on different visual parameters. The present inventors describe that these therapeutic effects are potentially mediated by the neuroplastic actions of these molecules, potentially at different levels of the visual pathways, from the retinal pigment layer (see ARPE-19 test results, Annex 3) to the retinal pigment layer. visual cortex (see in vitro results in neurogenesis, Annex 2). Thus, based on the observation work of the present inventors, the following conclusions were reached: a) Repeated daily administration of neuroplastic doses of 5-HT2A agonist substances is potentially safe and effective for vision improvement; b) Repeated daily administration of neuroplastic doses of 5-HT2A agonist substances is potentially safe and effective for the treatment of ophthalmological diseases and conditions associated with visual impairment; c) 5-HT2A agonists at neuroplastic doses may be therapeutic as single agents (eg psilocybin or psilocin or baeocystin) or may be therapeutic as a mixture of molecules, eg the mixture contained in the mushroom Psilocybe Atlantis: psilocybin and o psilocin and o baeocystin and mixtures thereof, including mixtures of other molecules contained in the sclerotia of Psilocybe atlantis; d) clinically significant and potentially medial therapeutic effects of chronic neuroplastic doses of 5-HT2A agonists last longer than the expected effects of receptor occupancy, pointing to a potential effect in modulating neural plasticity rather than an effect based on extemporaneous occupancy of the receiver; and e) Clinically significant medial effects of chronic neuroplastic doses of 5-HT2A agonists last longer than the expected effects of receptor occupancy, pointing to a potential therapeutic effect of chronic intermittent neuroplastic doses of 5-HT2A agonists. [*Drugs that act directly on neurotransmitters and their pathways, including transporter pathways, such as benzodiazepines and opioids (and also SSRIs), exert their effects by interacting with specific receptors and their effects cease or even rebound when discontinued the drugs. A persistence of effects, as indicated in the present inventors' cases of administration of chronic neuroplastic doses of 5-HT2A agonist substances, points to a potential effect modulated through other mechanisms (eg, croaon / Lznz / q / υιλι mechanisms of neural plasticity or biological trajectories) that endure receptor occupancy.] For drugs with a very short half-life in humans, as is the case with many 5-HT2A drugs, albeit in large doses (psychedelic doses) may result in rapid down-regulation of 5-HT2A receptors and loss of effect (eg, loss of psychedelic effect) on repeated dosing, chronic underdosing (non-psychedelic doses) may result in continued efficacy for minor or no down-regulation of receptors due to 1) less receptor occupancy 2) rapid drug clearance 3) effects on NMDARs (see Example 3, below). The above mechanisms may suggest an inverse U curve when 5-HT2A agonists are used as neuroplastics (to modulate neural plasticity in the absence of psychedelic / psychotomimetic effects): doses at the top of the inverted U curve (doses neuroplastic) are more effective than very extreme doses on the upward slope of the inverted U curve and also more effective than the dose on the downward slope of the inverted U curve. These observations suggest that clinically measurable effects on visual parameters can be obtained with repeated neuroplastic (non-psychedelic / non-psychotomimetic) doses of 5-HT2A agonist substances at doses that do not elicit psychedelic / psychotomimetic symptoms and such doses result in plasma levels of such substances much lower than the plasma levels generally required for psychedelic / psychotomimetic effect. EXAMPLE 2 in vivo studies The available scientific literature, both in clinical settings (safety and efficacy studies) and in experimental settings (in vitro and in vivo experimental settings, including the work by Ly et aL, 2018), has so far remained focused on treatments. acute pulse shocks with large doses of drugs expected and intended to produce clinically significant psychedelic / psychotomimetic effects (Johnson MI, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6 ):603-20). A similar approach (pulse exposure at high concentrations) has been taken in experimental trials (Ly et al., 2018) thus supporting the use of psychedelic doses of 5-HT2A agonists. To assess whether repeated chronic low-dose (non-psychedelic / psychotomimetic) administration of 5-HT2A agonists potentially modulates neural plasticity and / or modulates neuroinflammation, and to assess whether these effects are potentially cytoprotective, and whether these effects may result in potentially clinically significant therapeutic effects, the present inventors croaon / Lznz / q / υιλι performed a series of in vivo preclinical experiments. These trials were specifically designed to assess the potential therapeutic effects of neuroplastic chronic dosages of 5-HT2A agonists. 1 Effects of psilocybin in Rats Fed with Western Diet Hypothesis: Chronic low-dose psilocybin treatment counteracts the negative effects of the Western Diet (WD) on metabolic parameters. Background: The modern western lifestyle is characterized by the consumption of a hypercaloric diet rich in fat and simple carbohydrates. This diet is associated with obesity, type 2 diabetes mellitus (T2D) and metabolic syndrome (Lozano I, Van der Werf R, Bietiger W, Seyfritz E, Peronet C, Pinget M, Jeandidier N, Maillard E, Marchioni E, Sigrist S , Dal S. High-fructose and highfat diet-induced disorders in rats: Impact on diabetes risk, hepatic and vascular complications. Nutrition & Metabolism 2016, 13: 15). These metabolic disorders have been associated with other diseases, for example non-alcoholic fatty liver disease (NAFLD), but also with pathological conditions characterized by a low-grade inflammatory state, which could lead to severe immunological and neuropsychiatric dysfunctions (Castanon N , Lasselin J, Capuron L. Neuropsychiatric Comorbidity in Obesity: Role of Inflammatory Processes. Frontiers in Endocrinology, 2014, 5: 74). In the liver, lipid accumulation may be due to increased fatty acid supply or de novo lipogenesis, and / or decreased lipid clearance due to decreased lipid secretion or oxidation (Musso G, Cassader M, Gambino R. Non-alcoholic steatohepatitis: Emerging molecular targets and therapeutic strategies. Nature Review Drug Discovery 2016, 15: 249274). The accumulation of fatty acids in the liver results in the development of NAFLD, which currently represents one of the most common causes of chronic liver disease worldwide and one of the leading causes of liver-related morbidity and mortality, and, as previously established, it is strongly associated with the development of obesity, type 2 diabetes, and metabolic syndrome (Byrne CD, Targher, G. NAFLD: A multisystem disease. Journal of Hepatology 2015, 62: S47-S64). Although the relative contribution of the different pathways described above to the development of NAFLD is only partially known, a number of preclinical studies and clinical trials have shown that de novo lipogenesis plays a pivotal role in the development of NAFLD (Lambert JE, Ramos -Roman MA, Browning JD, Parks EJ. Increased de novo lipogenesis is a distinct characteristic of individuals with nonalcoholic fatty liver disease. Gastroenterology 2014, 146: 726-735). To date, although the prevalence of NAFLD and its complication, non-alcoholic steatohepatitis (NASH), are increasing worldwide, there are currently no therapeutic options available (Alkhouri N, Lawitz E, Noureddin M. Looking Into the Crystal Ball: Predicting the Future Challenges of Fibrotic NASH Treatment.Hepatology Communications 2019, 3:605-613). Methods: 30 male Sprague-Dawley rats (200±50 g) were housed 3 per cage at crooon / 1 znz / q / υιλι a temperature of 21°C, alternating 12 hours of light and 12 hours of darkness and after a period of adaptation were randomized into two groups. The control group (N: 10) continued on the Standard Diet (SD, Altromin, Italy), while the Western Diet (WD) group (N: 20) was switched to the High Fat Diet (HFD) (60 % kcal from fat, Altromin, Italy), enriched with fructose in drinking water, at a concentration of 30% (w / V). The combination of HFD and 30% fructose in drinking water is a model of the so-called WD. After 26 weeks, the rats in the WD were randomly divided into 2 subgroups (N=10) treated daily for 15 days by gavage respectively with aqueous vehicle or psilocybin (0.05 mg / kg body weight). All procedures involving animals were performed in compliance with institutional guidelines in compliance with laws and policies (Council Directive of the European Economic Community 86 / 609, OJ L 358, 1, Dec.12, 1987; NIH Guide for the Care and Use of Laboratory Animals, NIH Publication No. 85-23, 1985). The study design was approved by the Ethics Committee of the University of Padua for the care and use of laboratory animals and by the Italian Ministry of Health. Results: Glucose Tolerance Test Ora! Oral glucose tolerance test was performed the day before slaughter to assess the glycemic response after oral administration of glucose (2 g / Kg body weight). Referring to Figs. 1A and IB, in the WD + vehicle group, the oral glucose tolerance test induced a significant increase in the glycemic peak after 15 minutes of glucose probe compared to the SD group, although the curve of the WD animals + psilocybin was comparable to the SD group. Consequently, after the oral glucose tolerance test, the WD-induced increase in glycemic spike was counteracted by 15 days by gavage with psilocybin 0.05 mg / kg body weight compared to gavage with vehicle. Body and liver weight Referring now to Figs. 2A to 2C, at sacrifice, the present inventors observed an increase in body and liver weights in the WD+vehicle rats compared to the SD-fed rats and the WD+psilocybin rats. Notably, treatment with psilocybin of 0.05 mg / kg for 15 days was able to counteract this WD-induced increase in liver and body weight. Liver histology and liver inflammation To assess the condition of the liver, the present inventors performed histological analysis of liver tissue by hematoxylin-eosin staining of paraffin-embedded slices of liver. On histology, SD-fed rats showed normal crooon / Lznz / q / υιλι liver architecture (Fig. 3A), while lipid accumulation leading to hepatic steatosis was observed in WD-fed rats, where lipid accumulation lipids could be observed in 15% of hepatocytes (median) (Fig. 3B, white fat vesicles, see also Table 2, below), while a dramatic reduction in steatosis could be observed in WD rats treated with psilocybin (Fig. 3C, Table 2). croaon / Lznz / q / υιλι TABLE 2 Liver histology: hepatic steatosis plow. Data are expressed as median (range) Group % Hepatic macrovesicular steatosis Standard Diet 0(0) Western diet 15 (5-20) Western diet +psilocybin 5 (<5-15) Gene expression of three interleukins involved in inflammatory pathways was measured by qRT-PCR in rat livers. The results are shown in Figs. 4A to 4C. Gene expression of the pro-inflammatory and interleukin IL-6 was significantly increased by WD administration, indicating increased liver inflammation, and psilocybin treatment was able to counteract this effect, restoring physiological IL-6 levels. Regarding the anti-inflammatory interleukin IL-10, its gene expression increased in rats fed with WD, and decreased significantly in rats treated with psilocybin, without reaching normal levels. In addition, gene expression of CCL2, a chemokine involved in inflammation and immune cell recruitment in the liver, was increased by WD relative to SD, and psilocybin treatment did not significantly affect this increase, although a significant increase could be observed. decreasing trend in psilocybin-treated animals compared with untreated WD-fed rats. reactive oxygen species Since reactive oxygen species (ROS) production is related to hepatic oxidative and metabolic stress, eg hepatic lipid deposition, the present inventors evaluated ROS production in rat livers by means of the 2'-diacetate method. ,7'dichlorofluorescine (DCFDA). The results are shown in Fig. 5, and it was shown that hepatic ROS production was significantly increased by WD + vehicle administration, while WD + psilocybin treatment was able to restore physiological ROS levels. Hepatic lipid metabolism To confirm the histological data indicating the presence of hepatic steatosis, the present inventors measured the expression of two genes involved in lipid metabolism, ie, GPAT4 and SREPB2 by qRT-PCR. Referring to Figs. 6A and 6B, the gene expression of both GPAT4 and SREPB2 was significantly increased by WD + vehicle administration, whereas WD + psilocybin treatment was able to cause a significant drop in their expression, even if this drop did not restore their levels. physiological. This may indicate that psilocybin leads to a reduction in hepatic steatosis by reducing lipid accumulation and de novo lipogenesis in hepatocytes. behavior test To ascertain whether chronic low-dose psilocybin administration alters behavior in WD-fed rats, the present inventors performed the Locomotion Activity Test (LMA) before and after psilocybin treatment (see Figs. 7A to 7C). This test has the objective of evaluating the spontaneous locomotor activity in laboratory animals. This test is carried out in a gray arena (open field) exposed to light of regulated intensity (24 and 30 lux), avoiding light-shadow areas within the perimeter in which the experiment takes place. Along the base of the open field, 4 standard-size squares have been drawn, clearly visible even in the dark and large enough to allow the animal to remain inside them for their entire length. The LMA test was preceded by one hour of adaptation, at the end of which the rat was inserted into the open field, in one of the previously designed squares. Movements and behaviors in reaction to the environment were then recorded for 10 minutes. In the LMA test, three fundamental aspects were evaluated: 1. The number of crossings, that is, the number of crossings made by the animal from one square to another, passing through the line that defines them with both legs. This value gives an indication of the distance moved by the animal during the test and of its locomotor activity; 2. The number stood on two legs, that is, the number of times the animal stands on its two hind legs. This value is proportional to the state of anxiety experienced; 3. Grooming time, that is, the time interval spent by the animal in washing itself, another indicative value of the state of anxiety experienced during the test. As regards the number of crosses, the present inventors observed a decreasing trend in animals treated with psilocybin, which is similar to the results obtained with rats fed SD. This is probably due to repeating the croaon / Lznz / q / υιλι test after 2 weeks, but this effect could not be observed in WD-fed rats. The present inventors also observed a significant increase in grooming time only in rats treated with psilocybin. Of interest, there was no evidence of psychedelic behavioral effects of chronic low-dose (15-day) administration of 0.05 mg / Kg psilocybin. inflammatory diseases To ascertain whether the observed liver inflammation correlates with a systemic increase in inflammatory markers, we measured the plasma levels of two cytokines (IL-6 and TNFa) involved in inflammatory processes by ELISA kits (RayBiotech), following the manufacturer's instructions. . As shown in Figs. 8A and 8B, psilocybin administration dramatically decreased the plasma concentration of TNF-α relative to rats fed both standard (p<0.05) and Western (p<0.01) diets. Due to the high inter-individual variability, no significant differences in plasma IL-6 levels could be detected in the different groups, but a similar trend to the results observed for TNF-α levels was observed. 2. Effects on neurogenesis Hypothesis: Chronic low-dose psilocybin treatment counteracts the negative effects of the Western diet (WD) on neurogenesis. Background: Neurogenesis persists in two niches of the adult brain: the dentate gyrus of the hippocampus and along the lateral walls of the lateral ventricles, in the subventricular zone (SVZ) (Lepousez G, Nissant A, Lledo PM Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 2015;86:387-401; Lledo PM, Alonso M, Grubb MS Adult neurogenesis and functional plasticity in neuronal circuits. Nature reviews Neuroscience 2006;7:179193). Neurogenesis represents a mechanism of neuronal plasticity and can be affected by many factors (Redolfi N, Galla L, Maset A, Murru L, Savoia E, Zampara I, Gritti A, Billuart P, Passafaro M, Lodovichi C. Oligophrenin-1 regulates Number, morphology and synaptic properties of adult-born inhibitory interneurons in the olfactory bulb. Human Molecular Genetics 2016;25:5198-5211. hefort C, Gheusi G, Vincent JD, Lledo PM. Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory. The Journal of neuroscience: the official journal of the Society for Neuroscience 2002;22:2679-2689. Lepousez G, Nissant A, Lledo PM. Adult neurogenesis and the future of the rejuvenating brain circuits. Neuron 2015;86:387-401 Lledo PM, Saghatelyan A. Integrating new neurons into the adult olfactory bulb: joining the network, life-death decisions, and the effects of sensory experience Trends in Neurosciences 2005; croaon / 1 znz / q / υιλι 28:248-254. Recent studies report that obesity accelerates the aging process and suppresses neurogenesis, potentially leading to neuropsychiatric effects. The effect seems specific for the SVZ, since the generation of new neurons in the hippocampus does not seem to be affected (Ogrodnik M, Zhu Y, Langhi LGP, Tchkonia T, Kruger P, Fielder E, Victorelli S, Ruswhandi RA, Giorgadze N, Pirtskhalava T, Podgorni O, Enikolopov G, Johnson KO, Xu M, Inman C, Palmer AK, Schafer M, Weigl M, Ikeno Y, Burns TC, Passos JF, von Zglinicki T, Kirkland JL, Jurk D Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis. Cell Metabolism 2019, 29:1233). Methods: To perform immunohistochemistry, rats were euthanized and then perfused with 0.9% saline followed by 4% paraformaldehyde (PFA) in phosphate buffered saline IX (PBS) (n rats tot = 8, n = 2 for each condition). ). Rat brains were rapidly dissected and then post-fixed in 4% PFA for 48 hours. Brains were embedded in 2.5% agarose (Sigma-Aldrich) and then sectioned into sagittal sections (40 µm thick) on the vibratome (Vibratome VT1000S, Leica). Sagittal sections of the brain, including the subventricular zone, were treated with a blocking solution of 10% normal goat serum (Jackson ImmunoResearch) in PBS IX for 1 hour and then stained with rabbit antiK¡67 monoclonal antibody (Abcam, AB 16667) (1:200) overnight. The primary antibody was developed with Alexa Fluor 488-conjugated goat anti-rabbit (1:500, Jackson ImmunoResearch), applied for 2 hours at room temperature. Brain sections were mounted with Aqua-Poly / Mount (Polysciences). Images of the sagittal sections containing the subventricular zone were acquired under a confocal microscope (Zeiss LSM 700) equipped with an EC Plan-Neofluar 20X / 0.50 M27 objective (Zeiss). K¡67-positive cells were counted along the lateral wall of the lateral ventricles in sagittal sections of the rat brain, using ImageJ software (RRID: nif-000030467). Results Referring to Figures 8A to 8C, the present inventors found that neurogenesis was significantly reduced in WD-fed rats compared to SD-fed rats (WD-fed rats, new cells n-2722 ± 225; WD-fed rats). SD, new cells n = 4601 ± 17; WD vs. SD rats, unpaired t-test, p = 0.01). Psilocybin 0.05 mg / kg via gavage for 15 days was able to partially preserve the number of newly generated cells in WD-fed rats (psilocybin-treated rats, new cells n = 3404 ± 199) compared to WD-fed rats treated with vehicle. conclusions The results showed that chronic low-dose treatment with low-dose croaon / Lznz / q / υιλι psilocybin administered to WD-fed rats had a positive effect on several metabolic parameters, including glycemic control, liver lipid accumulation, weight body and inflammatory markers. The results also confirm that WD significantly reduces the number of newly generated cells in the SVZ. Furthermore, chronic low-dose psilocybin treatment is able to partially rescue the number of newly generated neurons in the SVZ of WD-fed rats and did not elicit signs of anxiety or psychedelic behavioral effects in rats. The following conclusions were also reached: a) Chronic administration of neuroplastic doses of 5-HT2A agonists is potentially safe and effective for the treatment of diseases and conditions; b) Chronic administration of neuroplastic doses of 5-HT2A agonists is potentially safe and effective for the treatment of diseases and conditions associated with impaired neurogenesis; c) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of diseases and conditions associated with learning disabilities, including poor school / academic performance, poor performance in motor skills, poor performance in dysfunctional social skills and emotional patterns (based on b); d) chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of psychiatric diseases, including psychiatric disorders as defined by DSM5 and ICD11 (based on b); e) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of neurological diseases and conditions, including neurodevelopmental and neurodegenerative diseases (based on b); f) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of diseases and conditions associated with impaired glucose tolerance, including diabetes mellitus; g) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of diseases and conditions associated with obesity, including its complications; h) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of diseases and conditions associated with NAFLD and NASH; i) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of diseases and conditions associated with inflammatory states of the liver, including NASH; and croaon / Lznz / q / υιλι j) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of diseases and conditions associated with systemic inflammatory states. The human equivalent dose (HED) to the rat dose used in the study of Example 2 (0.05 mg / Kg) is 0.0094 mg / Kg (Nair AB, Jacob S. A simple practice guide for dose conversion between animals and humans. J Basic Clin Pharm 2016;7(2):27-31), approximately 0.66 mg of psilocybin for a 70-Kg human, well below the lowest doses shown to be psychedelic: 0.045 mg / Kg, approximately 3.2 mg for a 70 kg human (Hasler F, Grimberg U, Benz MA, Huber T, Vollenweider FX. Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose-effect study. Psychopharmacology (Berl). 2004;172(2): 145-156.doi:10.1007 / s00213-003-1640-6). In an experiment by Davis et al., 1977, the startle reflex was measured in 7 groups of 10 rats each after intraperitoneal injection of saline or 0.25, 0.50, 0.75, 1.0, 2.0, 4.0, or 8.0 mg / kg psilocybin. . At 0.75-2.0 mg / kg but not at lower doses, psilocybin increased startle amplitude while high doses (4.0-8.0 mg / kg) depressed startle. (Davis M, Walters JK. Psilocybin: biphasic dose-response effects on the acoustic startle reflex in the rat. Pharmacol Biochem Behav. 1977;6(4):427-431). In a study by Rambousek et al., 2014, subcutaneous psilocin significantly impaired Carousel maze acquisition at both doses (1 and 4 mg / kg) (Rambousek L, Palenicek T, Vales K, Stuchlik A. The effect of psilocin on memory acquisition, retrieval, and consolidation in the rat. Front Behav Neurosci. 2014;8:180). In both of these studies (Davis et al., 1977 and Rambousek et al., 2014), the doses administered to rats were much higher than the chronic low doses of psilocybin tested in our study, 0.05 mg / Kg daily for 15 days. The present inventors' much lower doses, 0.05 mg / Kg, did not significantly alter the behavior of the rat, except for the increase in grooming time as detailed in the behavior section of Example 2. Although the increase in grooming time in rodents has been associated with anxiety, in the case of rats, and in the absence of other related anxiety behavior, the increase in grooming time may also be associated with a release of the anxiety-provoking stimulus (Nazareth Veloso AW, Filgueiras GB, Lorenzo P, and Estanislau C. Psychology & Neuroscience 2016, Vol. 9, No. 1, 91-104). In the case of the present inventors' study this relief could have been provided by low dose pslocybin treatment. Sengupta P. The Laboratory Rat: Relating Its Age With Human's. Int J Prev Med. 2013;4(6):624-630. According to Sagupta P, 2013, rats are very much in the mature stages of life and thus the preservation of neurogenesis in the WD + psilocybin group compared to the WD + vehicle group potentially suggests anti-senescence activity of the system. nervous croaon / Lznz / q / υιλι accelerated by the western diet. The experiment the present inventors detailed in Example 2, is especially revolutionary as it is the first in vivo experiment to show that chronic neuroplastogen dose administration of 5-HT2A agonists is potentially therapeutic for the treatment of diseases and conditions. EXAMPLE 3 in vitro studies To assess the mechanisms of potentially therapeutic effects and whether repeated chronic low-dose treatments with 5-HT2A agonists potentially modulate neural plasticity and / or modulate neuroinflammation, and to assess whether these effects are potentially cytoprotective, including against excitotoxicity and against inflammatory mediators, and finally whether these effects can result in potentially clinically significant therapeutic effects, the present inventors performed a series of in vitro preclinical experiments. These trials were specifically designed to assess the potential therapeutic effects of repeated doses of neuroplastics (low concentration) of drugs classified as 5HT2A agonists. 1. Effect of psilocin and psilocin-carbamate on NMDAR subunits and 5-HT2 receptor subtypes in ARPE19 cells Hypothesis: The membrane of retinal pigment cells (ARPE-19 cell line) expresses NMDARs and the 5-HT2A and 5-HT2C receptors. Psilocin reduces L-glutamate-induced cytotoxicity and modulates the transcription and synthesis of select NMDAR protein subunits. Background: The mechanisms underlying the potential efficacy of 5-HT2A agonists administered at high psychedelic / psychotomimetic dosages (single sessions) for depression have recently been linked to BDNF and mToR pathways and have been potentially linked to neural plasticity: Ly et al. demonstrate that psychedelic compounds such as LSD, DMT, and DOI increase the complexity of the dendritic tree, promote dendritic spinal growth, and stimulate synapse formation. These cellular effects are similar to those produced by the short-acting antidepressant ketamine and highlight the potential of psychedelics for the treatment of depression and related disorders (Ly C, Greb AC, Cameron LP, et al. Psychedelics Promote Structural and Functional Neural Plasticity Cell Rep 2018;23(ll):3170-3182). Ly et al., however, did not test psilocin / psilocybin, and did not test croaon / Lznz / q / υιλι low doses or low doses relative to higher doses. Methods and Results: Expression of NMDAR and 5-HT subtypes in ARPE-19 cells First, the present inventors evaluated the expression of three NMDAR subunits (NMDAR1, NMDAR2A, NMDAR2B) and two 5-HT2 subtypes (5-HT2A, 5-HT2C) by immunofluorescence coupled with confocal microscopy. 7,500 cells / well were plated in a 24-well plate on sterile glass coverslips. The next day, immunofluorescence analysis was performed. The following primary antibodies were used: anti-NMDARlA (Abcam, ab68144), NMDAR2A (Bioss, bs-3507R-TR), NMDAR2B (Bioss, bs-0222R-TR), 5-HT2A (Bioss, bs-12049R), 5-HT2A (Bioss, bs-12049R), -HT2C (Bioss, 2959R), and the goat anti-rabbit IgG secondary antibody (GeneTex, GTX213110-04). Images of immunostained cells were acquired by means of a Zeiss LSM 800 confocal microscope, using 63X magnification and can be seen in Figs. 9A to 9E. ImageJ software was used to quantify the intensity of the fluorescent signal. Effect of psilocin on the cytotoxicity induced by gigutamate To ascertain the effect of psilocin on L-glutamate-induced cytotoxicity in ARPE-19 cells, the present inventors performed a cell viability assay. For this experiment, ARPE-19 cells were seeded in a 96-well plate (7000 cells / well). They were left overnight in a 37° incubator with 5% CO2. The next day, the cells were pretreated with the psilocin solutions. After six hours all wells (with the exception of control cells) were replaced with the L-glutamate solution dissolved in control Tris-buffered saline (CSS). After 5 min, the exposure solution was thoroughly washed and replaced with standard culture medium, according to a protocol already described (Choi DW, Viseskul V., 1988. Opioids and non-opioid enantiomers selectively attenuate Nmethyl-D -aspartate neurotoxicity on cortical neurons. Eur J Pharmacol 155, 27-35). After 24 hours of standing time, cell viability was evaluated by means of the ATPIite kit following the manufacturer's instructions. The results can be seen in Fig. 10, and the present inventors observed that psilocin, tested at 3 different concentrations (ranging from 0.025 to 0.1 μΜ) counteracted the observed reduction in cell viability induced by L-glutamate treatment. Effect of psilocin on the expression of ia protein of NMDAR subunits and 5-HT2 receptor subtypes The present inventors performed additional immunocytochemical studies to ascertain whether psilocin induces the synthesis of select proteins that form NMDARs and select 5-HT receptor subtypes (5-HT2A and 5-HT2C). 7,500 cells / well were plated in a 24-well plate on sterile glass coverslips. The next day, cells were treated with either croaon / Lznz / q / υιλι μΜ psilocin for 24 hours followed by 5 days of rescue in standard culture medium or 0.5 μΜ psilocin for 6 consecutive days. After 6 days, immunofluorescence analysis coupled with confocal microscopy was performed with the primary and secondary antibodies described above. Referring to Figs. 11A to 11C, ARPE-19 cells exposed to 0.05 μΜ psilocin for 6 days showed a dramatic increase in NMDAR1 and NMDAR2A subunits. NMDAR2B subunits changed. In contrast, ARPE-19 cells exposed to 10 μΜ psilocin for 24 hours showed only a slight, non-significant increase in NMDAR1 and NMDAR2A. NMDAR2B subunits changed. Referring now to Figs. 11D to 11F, in general, less apparent treatment effect on NMDAR subunit expression could be observed when psilocybin-containing cell medium was replaced daily (96 hours total) or cells were treated alternating with / without medium. of psilocin every 24 hours (96 hours total). In particular, an increase in the expression of NMDAR1 and a decrease in the expression of NMDAR2B could be observed with an incubation of 0.05 μΜ that was carried out alternating with / without psilocin medium every 24 hours. In addition, the effect of a chronic treatment with psilocin-carbamate for 96 hours on NMDAR subunits was evaluated. As shown in Figs. 11D to 11F, a reduction in the expression of NMDAR2A and NMDAR2B was observed. Referring now to Figs. 11G to 111, the effect of co-incubation of 0.05 μΜ psilocin with an excess (30 μΜ) of the prototype NMDAR antagonist MK-801 was evaluated. In particular, as regards the expression of NMDAR1 and NMDAR2A, the reported increase after chronic psilocin treatment (Figs. 11A to 11C) was counteracted by MK-801-mediated inhibition (Figs. 11G to 111). On the contrary, a drop in the expression of NMDAR2B was observed under the same conditions. NMDAR1 expression was significantly increased in the case of alternate incubation or when the psilocin-containing culture medium was replaced daily. Referring now to Figs. 12A and 12B, by contrast, psilocin has virtually no effect on 5-HT2A receptor expression in ARPE-19 cells, although a decreasing trend could be seen after both acute and chronic exposure. The expression of 5-HT2C expression was increased after chronic psilocin treatment. Conclusions: Prevention of excitotoxicity and induction of NMDAR subunits by psilocin exposure in ARPE-19 cells signals modulation (down-regulation) of Ca2+ influx. Induction of selected NMDAR subunits signals effects on membrane expression of NMDARs (NMR1 subunits are required for membrane expression of NMDARs) and signals other selective actions of 5-HT agonists on NMDAR subtypes (A to D). These actions of psilocin point to potential therapeutic uses for chronic low-dose crooon / Lznz / q / υιλι (continuous or intermittent) therapy with 5-HT2A receptor agonists via modulation of NMDARs for diseases and conditions that potentially benefit from prevention of excitotoxicity and / or benefit from modulation of NMDAR and / or modulation of neural plasticity, including the diseases and conditions listed in the present application, including ophthalmological, psychiatric, metabolic and neurological diseases and conditions. The following conclusions were also reached regarding ARPE 19 cells: a) ARPE 19 cells express the NMDARs (qPCR and immunofluorescence analysis); b) ARPE 19 cells express 5-HT2A receptors (qPCR and immunofluorescence analysis); c) 5-HT2A agonists are not cytotoxic to ARPE-19 cells; d) High concentration of glutamate is toxic to ARPE-19 cells; e) 5-HT2A agonists exert cellular protection against excitotoxicity induced by high doses of glutamate; f) 5-HT2A agonists modulate NMDARs by modulating mRNA for NMDAR subunits and by modulating synthesis of NMDAR subunits; g) 5-HT2A agonist modulates NMDAR subunits at chronic neuroplastic doses and at intermittent chronic neuroplastic doses (low concentrations) more effectively compared to large doses (high concentrations) applied only once (high pulse concentrations); h) chronic administration of neuroplastic doses of 5-HT2A agonist and chronic administration of intermittent neuroplastic doses of 5-HT2A agonists are potentially effective for the treatment of diseases and conditions associated with NMDAR dysfunction; i) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially effective for the treatment of diseases and conditions associated with learning disabilities, including poor school / academic performance, poor performance in motor skills, poor performance in social skills and dysfunctional emotional patterns (NMDAR modulation, based on e and f); j) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of psychiatric diseases, including psychiatric disorders as defined by DSM5 and ICD11 (NMDAR modulation, based on e and f); k) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially safe and effective for the treatment of neurological diseases and conditions, crooon / Lznz / q / υιλι including neurodevelopmental and neurodegenerative diseases (NMDAR modulation, based on e and f ); and I) Chronic administration of neuroplastic doses of 5-HT2A agonist is potentially effective for the treatment of ophthalmological diseases and conditions (effects on ARPE-19, retinal pigment epithelial cells, based on e and f). Example 3 potentially suggests therapeutic uses for 5-HT receptor agonists via modulation of NMDARs and prevention of excitotoxicity. The finding that the synthesis of select NMDAR subunits is modulated by 5-HT2A agonists and their protective effects on excitotoxicity points to a potential allosteric blockade of NMDAR channels opened by these drugs, with reduced Ca2+ influx. toward physiological levels, prevention of excitotoxicity, and resumption of cellular function, eg, resumption of synthesis of NR-1 subunits. The present inventors also describe that even before mRNA induction and synthesis occurs, ER mobilization of NMDAR1 subunits induced by modulation of Ca2+ influx via NMDARs can result in cell membrane expression of new NMDARs. as also noted in the review by Baez et al., 2018 (Baez MV, Cercato MC, Jerusalemsky DA. NMDA Receptor Subunits Change after Synaptic Plasticity Induction and Learning and Memory Acquisition. Neural Plast. 2018). The present inventors have obtained additional allosteric modulation signals from the NMDAR pore (see Example 5) and are in the process of confirming this postulated mechanism of action by performing a FLIPR calcium assay experiment. The increase in NMDARs in the post-synaptic gap may also be associated with a decrease in peri-synaptic / extra-synaptic NMDARs. Although post-synaptic NMDARs located in synapses are associated with LTP and cell survival, extra-synaptic NMDARs have been associated with excitotoxicity and apoptosis. The positive effects of 5-HT2A agonists on cell survival (described in Example 3 and Example 4) and the positive effects of the combination of psilocin and dextromethadone on UV-induced senescence (see Example 6) may be due to downregulation of Ca2+ influx. Additional experiments are performed to test this mechanism for cell protection and increased survival. The new experiments presented with this application point to protection from excitotoxicity of 5-HT2A agonists and confirm the increases in NMDAR1 mRNA in retinal cells exposed to 5-HT2A agonists and also show that 5-HT2A agonists induce the synthesis of NR-2A subunits but not NR-2B subunits, signaling a potentially selective repair mechanism (selective for NMDAR subtypes) with synthesis of new select NMDAR subunits and expression of new select NMDAR subtypes and mechanism of potential synapse reinforcement (post-synaptic modulation of NMDARs), in addition to the BDNF-dependent effects described by Ly et al., 2018 that provide a croaon / Lznz / q / υιλι 100 mechanism for retrograde pre-synaptic enhancement and neurite outgrowth effects. Both pre-synaptic neuroplasticity effects, as shown by Ly et al., 2018, and post-synaptic enhancement, as noted by the present inventors' experiments on NMDAR subunit modulation, are essential for LTP, memory formation, and learning. EXAMPLE 4 Additional in vitro studies - Corneal Cells In vitro study on the cytotoxicity and anti-inflammatory effects of psilocin Objectives The study aims to verify: a) the effects of psilocin on cell viability b) the expression of NMDAR and HT2A subunits in corneal epithelial cells and keratocytes c) the anti-inflammatory effects of psilocin on corneal epithelial cells treated with the culture medium of activated human monocytes (line U937) that differentiate from macrophages d) the anti-VEGF and anti-fibrotic effects of psilocin in keratocyte cultures exposed to the inflammatory conditioned medium of activated U937 cells materials and methods Cell cultures. Human corneal epithelial cells (HCE) were obtained from the American Type Culture Collection. The U937 human monocyte cell line was purchased from Thermo Scientific. Primary corneal keratocirts were obtained after digestion from healthy donors purchased from the Veneto Eye Bank Foundation (Venezia Mestre, Italy). After the corneal epithelium was removed with a cell scraper and the endothelium was separated enzymatically using 0.05% trypsin / 0.02% EDTA solution for 15 minutes at 37°C, the stroma was then cut into 3- to 4-mm and treated overnight at 37°C with solutions of collagenase type I (100 U / ml) and hyaluronidase (2 mg / ml) in Dulbecco's Modified Eagle's Medium (DMEM). Isolated keratocytes were then seeded into monolayers and cultured at 37°C with 5% CO2 in DMEM containing 10% FBS, 1% penicillin-streptomycin (P / S) and 1% L-glutamine (otherwise known as full medium). The expanded cells were trypsinized and subcultured at a 1:2 ratio. Corneal cells were grown under standard cell culture practices in complete DMEM medium at 37°C, in a 5% CO2 atmosphere. U937 human monocytes were cultured in suspension in complete medium of RPMI 1640 se crooon / Lznz / q / υιλι 101 were passed through a dilution twice weekly using a seeding density of 106 cells / ml. Psilocin cytotoxicity and viability evaluations. Different concentrations of psilocin were added to corneal cells and cytotoxicity was determined 3 days later. Cell viability was assessed by the MTT test (3-4,5-dimethylthiazol 2-yl 2,5diphenyltetrazolium bromide, Sigma, MO, USA) at 1, 3, and 6 days after psilocin treatment, using a modified Denizot method. With this procedure, only viable cells with functioning mitochondria can oxidize MTT to a violet-red reaction product. Immunofluorescence coupled with confocal microscopy. 7,500 cells / well were plated in a 24-well plate on sterile glass coverslips. The next day, immunofluorescence analysis was performed. The following primary antibodies were used: antiNMDAR1A (Abcam, ab68144), 5-HT2A (Bioss, bs-12049R), 5-HT2C (Bioss, 2959R), and the goat anti-rabbit IgG IgG secondary antibody (GeneTex, GTX213110-04 ). Images of immunostained cells were acquired by means of a Zeiss LSM 800 confocal microscope, using 63X magnification. ImageJ software was used to quantify the intensity of the fluorescent signal. Evaluations of anti-inflammatory and anti-fibrotic effects. Cytokine expression was analyzed in human keratocytes and HCE cells exposed to the inflammatory conditioned medium (CM) of activated U937 cells. Human U937 monocytes differentiated into macrophages by treatment with 50 ng / mL phorbol myristrate acetate (PMA) for 48 h followed by exposure to 1 pL / mL lipopolysaccharide (LPS) for 1 hour. The cells were then washed and cultured with complete RPMI for 24 hours to produce the inflammatory SC. MC was collected, filtered and stored at -80°C. Monocyte to macrophage differentiation was examined under an inverted phase contrast microscope and mRNA expression of the macrophage differentiation marker CD68 was analyzed by real-time quantitative PCR ( qPCR). Then the cells were washed and cultured with complete DMEM for 24 hours to produce the MC. The CM was collected, filtered and stored at -80°C. Corneal cell cultures were exposed for 24h to activated U937 cell MC and then treated in the presence or absence of different concentrations of psilocin. Cytokine expression was analyzed in human keratocytes and HCE cells exposed to CM for 24h and then treated in the presence or absence of psilocin at different concentrations, using untreated cultures as controls. At 4 and 10 or at 4, 10 and 24 h, the cells were separated and mRNA was extracted to analyze the expression of pro-inflammatory cytokines (IL-1β, TNF-α, IL-8, IL-12, IFNy). The expression of type I collagen and VEGF was analyzed in mRNA extracted from keratocyte cell cultures. The experiments were performed three times. Statistic analysis. Graphpad Prism 8 was used for statistical analyses. Comparison between groups was performed using Student's unpaired t-test. The data is croaon / Lznz / q / υιλι 102 presented as mean and standard error. For statistical significance, differences were indicated at ^<0.05 (*), ^<0.01 (**) and ^<0.001 (***). Results Effects of psilocin cytotoxicity and viability in HCE cells and keratocytes. Corneal cells were cultured separately with different concentrations of psilocin (from 000.1 to 100 μΜ) and cytotoxicity was evaluated 3 days after treatment (Figs. 13A and 13B). Cell viability was analyzed by the MTT test up to 6 days and as shown in Figs. 14A and 14B, significant increased viability was found in both HCE cells and keratocytes in the concentration range of 0.1 to 1 μΜ psilocin. Expression of the NMDAR1, 5-HT2A and 5-HT2C proteins in HCE cells and keratocytes. HCE cells express NMDAR1 and both serotonergic receptors 5-HT2A and 5-HT2C while keratocytes do not express NMDAR1 and 5-HT2C at significant levels (see Figs. 15A to 15D). Effect of psilocin on the expression of some pro-inflammatory cytokines by corneal cells cultured in the conditioned medium (CM) of U937 monocytes activated by PMA. Since it has been shown that native corneal cells are activated after stromal injury and inflammation, the present inventors analyzed the expression of some pro-inflammatory cytokines in corneal cells treated with the MC of activated U937 monocytes (macrophages). qPCR analysis of mRNA extracted from PMA-activated U937 cells showed highly increased expression levels of the macrophage differentiation marker CD68. Exposure of corneal cells to macrophage MC confirmed that the environment created by macrophages greatly increased the expression of pro-inflammatory cytokines in corneal cell cultures. Subsequently, to verify the influence of psilocin on the production of pro-inflammatory cytokines, the molecule was added to cells at a concentration of 0.1 or 1 μΜ. qPCR analysis demonstrated that treatment of keratocytes with PMA-activated U937 cell MC induced significant over-expression of IL-Ιβ, IL-8 and IL-12 mRNA (Figs. 16A to 16D). The presence of 0.1 and 1 μΜ psilocin induced a significant decrease in the expression of IL-Ιβ at 4 h (Fig. 16A) and of IL-8 (Fig. 16B) and IL-12 (Fig. 16C) at 4 and 10 h post-treatment. TNF-α expression was very low and comparable to that of cells treated with CM alone (Fig. 16D). IFNγ expression was not detectable in the present inventors' qPCR assays. Gene expression of VEGFI (Fig. 17) and type I collagen did not change significantly in keratocyte cultures treated with U937-activated MC and subsequently cultured in the presence of 0.1 and 1 μΜ psilocin for 4, 10, and 24 h. Gene expression of pro-inflammatory cytokines IL-Ιβ, IL-8, IL-12 and TNF-α was much less evident in HCE cells treated with the same MC of monocytes activated with U937 croaon / Lznz / q / υιλι 103 (Figs. 18A to 18D). In addition, a significant down-regulation of gene expression was observed only for IL-8, after 10 h of treatment, in the presence of 0.1 and 1 μΜ psilocin. conclusions This study demonstrated that psilocin does not have a cytotoxic effect in vitro at concentrations between 0.001 and 10 μΜ. Additionally, psilocin induced a significant increase in corneal cell viability in vitro at 3 and 6 days after treatment at concentrations of 0.01, 0.1, and lpM. Furthermore, at the concentration of 0.1 pM and 1 pM, psilocin exerts anti-inflammatory effects on keratocytes and HCE cells that could be therapeutic for the anti-inflammatory treatment of ocular disorders (O.OlpM was not tested in this experiment). The gene expression of VEGF I (Fig. 17) and type I collagen did not change significantly in the keratocyte cultures treated with U937-activated CM and therefore an anti-fibrotic effect of the molecule could not be demonstrated in this model. Alternative studies should be considered to better evaluate the anti-fibrotic effects of psilocin on corneal cells using other models of inflammation or different inflammatory stimuli. Signaling pathways controlled by psilocin should also be analysed. Additionally, based on the study of this Example, the present inventors concluded: a) HCE cells express NMDAR and 5-HT2A receptors; keratocytes express 5-HT2A receptors (qPCR and immunofluorescence assay); b) 5-HT2A agonists are not cytotoxic; c) 5-HT2A agonists potentially increase cell viability at neuroplastic doses (0.01 and 0.1 microM); d) 5-HT2A agonists are potentially effective for the treatment of inflammatory states; and e) 5-HT2A agonists are potentially effective for the treatment of dry eye diseases and dry eye syndrome. Of interest, the regulation of Ca2+ influx through NMDAR may be the mechanism by which cell viability is increased (Liu ZY, Zhong QW, Tian CN, Ma HM, Yu JJ, Hu S. NMDA receptor-driven calcium influx promotes ischemic human cardiomyocyte apoptosis through a p38 MAPK-mediated mechanism. J Cell Biochem. 2019;120(4):4872-4882). EXAMPLE 5 Molecular Modeling crooon / 1 znz / q / υιλι NMDAR modulation by 5-HT2A agonists, including induction of 104 selected NMDAR subunits and the prevention of L-glutamate-induced excitotoxicity (as described in Example 3), potentially points to an allosteric interaction that downregulates excessive Ca 2+ influx via the pore of excessively open NMDAR channels. Allosteric interaction might also play a role in the actions of NMDAR antagonists known to also have an effect on serotonin pathways (for example, racemethorphan and its isomers, levomethorphan and dextromethorphan, methadone and its isomers, levomethadone and dextromethadone (Codd et al.). al. 1995), ketamine (du Jardín K.G., Liebenberg N., Müller H.K. et al. Differential interaction with the serotonin system by S-ketamine, vortioxetine, and fluoxetine in a genetic rat model of depression. Psychopharmacology 2016; 233, 2813- 2825), and memantine (Onogi H, Ishigaki S, Nakagawasai O, et al. Influence of memantine on brain monoaminergic neurotransmission parameters in mice: neurochemical and behavioral study. Biol Pharm Bull. 2009;32(5):850-855). In contrast, the modulation of NMDAR by 5-HT2A agonists and Structurally Modified Serotonergic Neuroplastics (SMSNs) could be due to the same mechanism postulated by known pore channel blockers, and could therefore be due to an interaction in the portion intra-membrane NMDAR. The present inventors tested this second hypothesis, direct interaction of 5-HT2A agonists and SMSNs with the in situ channel pore by molecular modeling investigations of selected 5-HT2A agonists and the binding of SMSNs to the transmembrane site of the GluNl-GluN2B tetrameric subtype NMDA receptor in its closed state. The computational NMDAR subtype constructed for in situ testing is the GluN1-GluN2B tetramer composed of 2 GluN1 subunits and 2 GluN2B subunits. Of interest the N2B subunits are essential for the formation of super-complexes that include NMDARs. To improve the computational efficiency of the calculations, only the transmembrane region of the receptor, where the putative PCP binding site is located, and where the tested FDA-approved clinically tolerated NMDA antagonists (dextromethorphan, ketamine, memantine), and where the present inventors hypothesize that 5-HT2A agonists and their derivatives (SMSNs) may also act. The present inventors used the structure identified by the Protein Data Bank (PDB) code 4TLM as the starting point for computational studies to investigate the drugs shown in Table 1A and positive controls (ketamine, memantine, dextromethorphan, amantadine, MK-801, PCP all known as NMDA open channel blockers that are supposed to act at the PCP site in the transmembrane domain with known affinities and known clinical effects PCP is a schedule I drug and MK- 801 is an antagonist with serious side effects that preclude its clinical use.The other four drugs are in clinical use and FDA-approved for various indications, as indicated throughout the application.As seen in Table IB, the Anchor scores for many of the SMSNs are crooon / Lznz / q / υιλι 105 at a similar interval as those of the established NMDAR channel jammers shown in Table 3 below. cpooon / Lznz / q / υιλι TABLE 3 Molecule Predicted Affinity (coupling) (Delta G, kcal / mol) MK-801 -6.8 PCP -6 Ketamine -5.8 Memantine -5.8 Amantadine -5.23 Dextromethorphan -6.3 Most of the compounds tested show predicted affinity results (anchoring results, Table IB) in a similar range to compounds with known NMDAR-blocking actions (predicted affinity of -5 -7, Table 3). These in situ results point to the potential blocking effects of NMDAR in the pore channel for 5-HT2A compounds and selected SMSNs. The present inventors are now planning initial dynamic modeling and calcium assays of FLIPR in vitro to better define and quantify the NMDAR-blocking actions of the Table 1A molecules. These in siiico results point to the potential blocking effects of NMDAR in the pore channel for 5-HT2A compounds and selected SMSNs. EXAMPLE 6 Antisenescence Effects The present inventors tested the antisenescence effects of psilocin and dmethadone on UVB-induced senescence in IMR-90, passage 20. Seeding occurred on day 1, with pretreatment on day 2, and UVB induction and retreatment on day 3, SABG on day 8, and microscopy (SABG) on day 9. The antisenescence effect was observed with 10 nM psilocin in combination with 10 nM d-methadone with a 34% reduction in Beta Gal positive cells. Higher doses of psilocin (up to 24 microM, experiment not shown) and lower doses (5nM, from this Example 6), showed no antisenescence effects. The results for Example 6 can be seen in Figs. 19A to 27D, and Tables 4, 5, and 6 below. 106 TABLE 4 Beta Gal assay Experiment 3: Analysis of the antisenescence effect of D-methadone and Psilocin on senescence induced by UVB IMR-90 cell line, passage 20 Drug concentration 1OnM 500nM D-methadone 1OnM + 5nM Psilocin 500nM + 5nM Psilocin Psilocin 5 nM lOnM + D-methadone 10 nM croaon / Lznz / q / υιλι TABLE 5 Beta Gal Assay (raw data) Compounds Concentra tion (nM) Wall Duplicate Total Number of Cells Bat a Gal ° / o %Aver SEM ° / oTot al No UVB 101. 32 (1) 1 39 4 10,256 41 15,984 11 3,1509 4 61,324 79 2 34 7 20,588 24 2 1 46 5 10,869 57 2 27 6 22,222 22 UVB without treatment 0 101. 32 (1) 1 41 35 85,365 85 85,635 14 2.8770 47 72,811 06 2 41 32 78,098 78 2 1 47 41 87,234 04 2 37 34 91,891 89 D methadone 10 1 1 32 23 71,875 79,008 07 2,9463 93 81,294 96 2 35 30 85,714 29 2 1 57 4 4 77.192 98 2 32 26 81.25 500 1 1 35 29 82.857 14 83.336 83 3.1322 2 83.939 39 2 17 14 82.352 94 2 1 34 26 76.470 59 2 36 33 91.666 67 10+ Psilocin 5 1 1 45 39 86.666 67 82.085 39 5.2389 7 87.410 07 107 nm 2 35 24 68.571 43 2 1 30 24 80 2 29 27 93.103 45 500+ Psilocin 5 nm 1 1 37 35 94.594 59 92.591 7 1.2728 72 73.868 31 2 37 3 5 94,594 59 2 1 28 25 89,285 71 2 37 34 91,891 89 croaon / Lznz / q / υιλι TABLE 6 Beta Gal Assay (raw data) Compiles Concentration (nM) Paired Duplicate Total Number of Cells Bat a Gal % %Aver SEM %Tot al Psilocin 5 1 1 20 15 75 82,299 78 2.6496 43 64,453 13 2 21 18 85,714 29 2 1 33 27 81,818 18 2 30 26 86,666 67 10 + D methadone 10 nm 1 1 34 14 41,176 47 51,778 45 3,6959 66 51,973 68 2 46 26 56,521 74 2 1 44 23 52,272 73 2 28 16 57,142 86 2 37 35 94,594 59 2 1 28 25 89,285 71 2 37 34 91,891 89 108 EXAMPLE 7 Psilocin-carbamate 1 Effects of isoleucinyl carbamate in young, adult and old mice fed high fructose Hypothesis: Chronic low-dose treatment with psilocin-carbamate (isoleucinyl carbamate) is well tolerated and improves cognitive and metabolic performances of high fructose-treated mice of different ages. Background: Psilocybin is believed to act as a prodrug for psilocin (Jacob III, P.; Shulgin, A.T. in NIDA Research Monograph 146 (Hallucinogens, an Update), 2000, Eds. Lin, G.C.; Glennon, R.A., pp. 74), as it is dephosphorylated in vivo by alkaline phosphatase to the active compound psilocin. Furthermore, psilocin chemically degrades rapidly in the presence of air, heat, and / or light, due to the presence of the free 4-hydroxy group on the tryptamine scaffold, which is susceptible to oxidation. On the other hand, psilocybin is much more stable than psilocin due to the presence of a phosphate ester, which protects the 4-OH group from both chemical and metabolic degradation. Thus, the prodrug approach can be considered a smart strategy to overcome the limitations of psilocin and obtain sustained plasma levels of psilocin after administration of the more stable psilocybin molecule. The present inventors herein evaluated the efficacy and safety of a new psilocin-carbamate (isoleucinyl carbamate) prodrug in which the 4-hydroxyl moiety is reversibly protected as a carbamate ester linked to the N-terminus of an isoleucine. Lipophilic amino acid carbamate ester prodrugs of phenolic compounds have been shown to strongly enhance bioavailability, by increasing absorption after oral administration, reducing metabolism, and leading to sustained release, up to 24 hours, of low concentrations. of the compound active particularly in brain tissue (See, for example, Azzolini et al. (2017) Eur J Pharm Biopharm volume 115, pages 149-158). A sustained-release formulation of the active psilocin compound with lower Cmax and Tmax concentrations could represent an advantage for safe pharmacological uses of psilocin by potentially avoiding the psychedelic / psychotomimetic effects of psilocin and psilocybin administration (which are dependent on reaching certain plasma concentrations as described in the present application) while potentially maintaining the ability to promote both structural and functional plasticity in brain tissue. Therefore, the present inventors designed, synthesized, and administered this novel drug, isoleucinyl carbamate, designed to young, adult, and old mice fed a standard diet enriched with 30% crooon / Lznz / q / υιλι 109 fructose in drinking water to obtain information about i) the preliminary toxicological profile of this psilocin prodrug in mice of different ages; ii) preliminary signals about its potential efficacy for the treatment of diseases and conditions. In particular, the effect of psilocin-carbamate administration on cognitive behavior and some synoptic markers was evaluated, since recent studies reported that obesity and the consumption of diets enriched with fat and sugar accelerate the aging process and potentially lead to neuropsychiatric effects. (Ogrodnik M, Zhu Y, Langhi LGP, Tchkonia T, Krüger P, Fielder E, Victorelli S, Ruswhandi RA, Giorgadze N, Pirtskhalava T, Podgorni O, Enikolopov G, Johnson KO, Xu M, Inman C, Palmer AK, Schafer M, Weigl M, Ikeno Y, Burns TC, Passos JF, von Zglinicki T, Kirkland JL, Jurk D. Obesity-Induced Cellular Senescence Drives Anxiety and Impairs Neurogenesis. Cell Metab 2019;29:1233, 2019). Methods: Male C57BL / 6 mice of different ages (young: 2 months old, adult: 5 months old, old: 18 months old) were housed 4 per cage at a temperature of 21°C, alternating 12 hours of light and 12 hours of darkness Mice were fed standard diet and fructose (30% w / v in drinking water) was added to their diet 4 days prior to randomization. Then, the mice were randomly divided into 2 subgroups by age (N=2 animals per group) treated daily for 15 days by gastric tube respectively with aqueous vehicle or psilocin carbamate (0.05 mg / kg body weight). All procedures involving animals were performed in compliance with institutional guidelines in compliance with laws and policies (Council Directive of the European Economic Community 86 / 609, OJ L 358, 1, Dec.12, 1987; NIH Guide for the Care and Use of Laboratory Animals, NIH Publication No. 85-23, 1985). The study design was approved by the Ethics Committee of the University of Padua for the care and use of laboratory animals and by the Italian Ministry of Health. Results: During the experiment, the animals were carefully monitored each day for a period not exceeding the maximum experimental endpoints. Access to water (30% w / v fructose) and food ad libitum was allowed. No obvious clinical symptoms were observed during the experimental period. No signs of toxicity or mortality were observed during the 14 days of administration of psilocin-carbamate or vehicle via gastric tube. Body and liver weight Referring to Figs. 28A and 28B, at sacrifice, the present inventors observed a decrease in body weight (p<0.05) and liver in adult mice treated with psilocin-carbamate. Remarkably, the same trend could be observed in old mice, while psilocin-carbamate treatment has no effect on body and liver weights croaon / Lznz / q / υιλι 110 of young mice. Blood glucose Before sacrifice, the present inventors measured the blood glucose concentration of the mice after a 2-hour fast. The present inventors did not observe statistically significant differences between the groups, although Fig. 29 shows that young mice have higher blood glucose levels than adult and old mice, and psilocin carbamate has no effect on blood glucose control. blood. A trend toward lower blood glucose concentration was observed in the old mice treated with psilocin carbamate. behavior test To ascertain whether chronic low-dose administration of psilocin-carbamate alters behavior in the mice tested, the present inventors performed the Locomotion Activity Test (LMA), the Novel Suppressed Feeding (NSF) test, and the adaptation / Olfactory maladjustment before and after psilocin-carbamate treatment. The LMA has the objective of evaluating the spontaneous locomotor activity in laboratory animals. This test is carried out in a gray arena (open field) exposed to light of regulated intensity (24 and 30 lux), avoiding light-shadow areas within the perimeter in which the experiment takes place. Along the base of the open field, 4 standard-size squares have been drawn, clearly visible even in the dark and large enough to allow the animal to remain inside them for their entire length. The LMA test was preceded by one hour of adaptation, at the end of which the rat was inserted into the open field, in one of the previously designed squares. Movements and behaviors in reaction to the environment were then recorded for 10 minutes. Three fundamental aspects were evaluated: 1. The number of crossings, that is, the number of crossings made by the animal from one square to another, passing through the line that defines them with both legs. This value gives an indication of the distance moved by the animal during the test and of its locomotor activity; 2. the number of standing on two legs, that is, the number of times the animal stands on the two hind legs. This value is proportional to the state of anxiety experienced; and 3. the grooming time, that is, the time interval spent by the animal in washing itself, another indicative value of the state of anxiety experienced during the test. Referring to Figs. 30A to 30C, as far as the number of crosses is concerned, the present inventors observed a decreasing trend in the post-treatment test of both treated and untreated mice. This is probably due to the adaptation of the animals to the test. The same observation could be made for the two-legged stander, while croaon / Lznz / q / υιλι 111 grooming was generally not affected by adaptation. Only in old mice a trend of increased (p=0.089) time spent grooming could be observed in mice treated with psilocin-carbamate. Of interest, there was no evidence of psychedelic behavioral effects of chronic low dose (14 day) administration of 0.05 mg / kg psilocin-carbamate (isoleucinyl carbamate). The Novel Suppressed Feeding (NSF) test was performed to assess the stress and hunger of mice after an overnight fast according to a protocol already described (Blasco-Serra et al., 2017). The arena in which the test was carried out was illuminated with a greater intensity of light in the center and less in the periphery. In the center of the arena a platform was placed, consisting of a Petri dish with a paper disk and a feeding pellet. After fasting for at least 12 hours, the animals were subjected to adaptation for 60 min before starting the experiment, to adapt to the new environment and minimize stress. Then, each mouse was placed in the arena and its behavior was monitored for a maximum of 10 minutes. When the mouse finally reached and began to eat the pellet, it was moved to another standard cage for 5 min, with a readily available feeding pellet. In this test, three parameters are normally measured: 1. The time required for the animal to start eating the feed pellet in the first cage (maximum time=10 minutes); 2. The number of times the mice sniff and approach the pellet in the first cage; and 3. The amount of pellet eaten by the animal in the second cage in 5 minutes. The results can be seen in Figs. 31A to 31C. In the olfactory adaptation / maladaptation test, the mouse is repeatedly presented with many odors, which are presented three times for two minutes each time. The investigator carefully records the time spent sniffing toward the odor as the measure of the olfactory response. A typical mouse shows a decreased response to odor with repeated presentations (so-called adaptation). The experienced then presents a novel odor that produces a sniffing catkin (maladaptation). After repeated presentation of the novel odor the animal again shows adaptation. The protocol used in this study involves the presentation of water, two non-social odors (almond and banana), and two social odors. Referring to Figs. 32A to 32F and Figs. 33A to 33F in general, responses to this test were characterized by wide variability. Overall, no significant effects could be observed after psilocin-carbamate treatment. 2. Effects of psilocin-carbamate treatment on NMDAR and synaptic markers Hypothesis: Chronic low-dose treatment with psilocin-carbamate (isoleucinyl carbamate) modulates neuroplasticity. crooon / Lznz / q / υιλι 112 Background: Certain serotonergic psychedelics have been shown to be able to significantly increase neuritogenesis and / or spinogenesis both in vitro and in vivo (Ly C, Greb AC, Cameron LP, et al. Psychedelics Promote Structural and Functional Neural Plasticity. Cell Rep. 2018; 23(ll):3170-3182). These changes in neuronal structure are accompanied by increased synapse number and function. Methods: Mice were euthanized by cervical dislocation. Immediately after sampling, fresh tissues isolating 4 brain regions (cerebellum, lateral cortex, olfactory bulb, and the remaining brain) were cut, rapidly collected, and placed in cryoflasks in liquid nitrogen and kept at -80°C. Brain tissues were lysed with RIPA lysis regulator (Invitrogen) and 1% (v / v) protease and phosphatase inhibitor cocktail (Sigma). Proteins were extracted by centrifugation at 14,000 rpm at 4°C for 30 minutes. The Bicinchoninic Acid (BCA) Assay kit (1113 Thermo-Scientific catalog #23225) was used to determine protein concentration following the manufacturer's instructions. Western blot analyzes were performed to determine NMDAR 1 (primary antibody: Abcam, ab68144), PSD95 (Bioss, bs-0179R-TR), p70 (Bioss, bs-3498R-TR) and synapsin 1 protein expression (Bioss , bs-3501R-TR) using 30 pg per band of nuclear or lateral cortex lysates, SDS-PAGE was performed on 8% polyacrylamide gels in reducing denaturing condition and proteins were transferred to a nitrocellulose membrane. 0.45 pm (BioRad Laboratories). The signal intensity of the immunoreactive bands was analyzed by Quantity One software (Bio-Rad Laboratories S.r.l.) and normalized to that of the loading control GAPDH. Results: The present inventors analyzed the protein expression of NMDAR1, PSD95, p70 and synapsinal in the lateral cortex of young, adult and old mice. Referring to Fig. 34, the expression of NMDAR1 tended to increase in young and old mice after psilocin-carbamate (isoleucinyl carbamate) treatment, whereas it tended to decrease in adult mice. It must be appreciated that a high inter-group variability could be observed. The present inventors also measured protein expression of the three synaptic proteins PSD95, p70 and synapsin 1. Referring to Figs. 35A to 35C, no significant differences in the expression of these proteins could be observed. However, PSD95 showed a different trend in juvenile and adult mice, as it tended to increase in juvenile mice and decrease in adult mice after treatment, similar to the NMDAR1 subunit. In contrast, synapsinal expression tended to increase only in croaon / 1 znz / q / υιλι 113 adult mice after treatment. Unexpectedly, p70 might not be detected in adult mice. Conclusions: Psilocin-carbamate (isoleucinyl carbamate), a prodrug of psilocin, appears to be safe and well tolerated when administered at a dose of 0.05 mg / kg daily for 14 days to young, adult, and old mice. Safety and tolerance were also confirmed by behavioral observation. Isoleucinyl carbamate potentially modulates synoptic proteins; these effects need to be better elucidated with larger experiments. Based on these preliminary results, the present inventors can now plan experimental studies aimed at better characterizing the PK and PD parameters of psilocin-carbamate, and obtain additional data about potential safety and efficacy for the treatment and prevention of diseases and conditions. The results are in line with those of the LMA test, showing that the mice are probably undergoing adaptation after the first test. There appears to be no effect of psilocin-carbamate on their performance on the NSF test. Some trends in the amount of food eaten in the second cage in 5 minutes by adult mice could be observed, as the decrease observed for the control group was counteracted by the psilocin-carbamate treatment. In summary, in vivo effects on neurogenesis, metabolic parameters and inflammation (as seen in Example 2, rat study), in vitro actions on NMDAR subunits (as seen in Example 3, ARPE study -19) and on cell viability (as seen in Example 4, corneal cells), clinical observations in human subjects (as seen in Example 1) and in situ results (as seen in Example 5, modeling) the in vitro anti-senescence results (as seen in Example 6) and this Example 7 mouse experiment with psilocin-carbamate are complementary in pointing out that chronic, continuous or intermittent administration of 5-agonist drugs HT2A and its derivatives listed in Table 1A at neuroplastic dosages (non-psychedelic / psychotomimetic dosages) exert potentially therapeutic actions in the modulation of NMDAR, neural plasticity, inflammation, metabolic parameters, and cell viability for the treatment and prevention of diseases and conditions. The present inventors therefore describe the use of 5-HT2A agonists and their derivatives (SMSNs) listed in Table 1A, alone or in combination with NMDAR channel-opening blockers, administered at non-psychedelic / psychotomimetic doses, repeatedly for days. o months o chronically, continuously or intermittently, for the treatment of diseases and conditions, especially for patients who could potentially benefit from well-tolerated drugs with effects on modulating neural plasticity over time and on modulating NMDARs crooon / 1 znz / q / υιλι 114 without clinically significant side effects, including, especially, without psychedelic / psychotomimetic side effects. Although the present invention has been described with reference to the details of the preferred embodiments of the invention, it is to be understood that the description is intended in an illustrative rather than a limiting sense, as it is contemplated that modifications will readily occur to those skilled in the art. in the art, within the spirit of the invention and the scope of the appended claims.

Claims

1. A compound comprising a structural analogue to psilocin, norpsilocin, psilocybin, baeocystin, norbaeocystin or L / ,V-dimethyltryptamine, according to formula I: croaon / Lznz / q / υιλι wherein Ri and Rz are, independently, hydrogen, deuterium, C1-C8 alkyl, C2C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 cycloalkenyl (independently or ring closure with nitrogen), aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate;R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, and nitrate;R4 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, any of which is optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or R4 is selected from the group consisting of alkyl ester, formyl, hydroxy, arylamido, alkylamido, alkylcarbamoyl, arylcarbamoyl, amino, alkylsulfonyl, and alkylamino;R5 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate;Rs is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl any of which is optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or Re is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, nitrate, -OP(O)(OH)2, -OC(O)R7, -OSO2OH, -OC(O)NHR7, -OC(O)NR7R8 and -SONH; yn is 1 to 5.; 2.- A compound comprising a structural analogue to 2,5-Dimethoxy-4-iodoamphetamine, according to formula II: croaon / Lznz / q / υιλι where A is C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene; Ri and R2 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 cycloalkenyl (independently or ring closure with nitrogen), aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate;R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, and nitrate;R4 and Rs are, 117 independently, hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or FU and Rs are, independently, selected from the group consisting of alkyl ester, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, and nitrate;and Re represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate.

3. A compound comprising a structural analogue to lysergic acid diethylamide, according to formula III: crooon / Lznz / q / υιλι wherein Ri and R2 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl (independently or ring closure with nitrogen), C3-C8 cycloalkenyl (independently or ring closure with nitrogen), aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate;R3 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or R3 is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, and nitrate;R4 and R7 are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; Rs and Re are, independently, hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate;or Rs and Re are, independently, selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, and nitrate; and Rs represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate. 4.- A compound comprising a structural analogue to ibogaine, according to formula IV: croaon / Lznz / q / υιλι O R3 wherein Ri is deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted in one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate;R2 is hydrogen, deuterium, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally 119 substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or FU is selected from the group consisting of halogen, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryloxy, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, and nitrate;R3 is hydrogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate; or R3 is selected from the group consisting of alkyl ester, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, and nitrate;and R4 represents 1-3 substituents selected from the group consisting of hydrogen, deuterium, halogen, C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, aryl or heterocyclyl, optionally substituted at one or more positions by deuterium, halogen, alkyl, alkyl ester, hydroxy, alkoxy, carboxy, formyl, aryl, aryloxy, heterocyclyl, amino, alkylamino, arylamido, alkylamido, thiol, thioalkyl, thioaryl, alkylsulfonyl, alkylcarbamoyl, arylcarbamoyl, nitro, cyano, or nitrate. 5 - The use of a compound of any of claims 1 to 4 in the manufacture of a medicament for preventing or treating diseases and conditions or for improving functions in patients or subjects, wherein the medicament is adapted to be administered at doses, dosages, posology, or formulations devoid of clinically significant psychedelic or psychotomimetic actions or effects, and having clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / ml or less, or human CNS 5HT2A receptor occupancy of 50% or less, or PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes.

6. Use as claimed in claim 5, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 2 ng / ml or less or human CNS 5-HT2A receptor occupancy of 40% or less.

7. Use as claimed in claim 5, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 1 ng / ml or less or human CNS 5-HT2A receptor occupancy of 30% or less.

8. Use as claimed in claim 5, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 120 minutes.

9. Use as claimed in claim 5, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 180 minutes.

10. The use as claimed in claim 5, wherein the administration of the croaon / Lznz / q / uili 120 compound occurs under conditions that can modulate NMDARs and their subunits in addition to modulating 5-HT2A receptors. 11.- The use as claimed in claim 5, wherein administration of the crooon / Lznz / q / uili compound can provide protection from excitotoxicity. 12.- The use as claimed in claim 5, wherein administration of the compound can modulate neurogenesis.

13. The use as claimed in claim 5, wherein the administration of the compound occurs under conditions effective for including modulation of neural plasticity. 14.- The use as claimed in which the substance exerts neuroplastic effects, claim 5, wherein the administration of the compound is repeated for days or months or is chronic. 15.- The use as claimed in claim 5, wherein the administration of the compound is intermittent and occurs every second day, every third day, every third week, every two weeks, or every third month.

16. The use of a 5-HT2A agonist substance in the preparation of a drug to prevent or treat diseases and conditions or to improve functions in patients or subjects, wherein the drug is adapted to be administered at doses, dosages, posology, or formulations devoid of clinically significant psychedelic or psychotomimetic actions or effects, and which have clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / ml or less, or human CNS 5-HT2A receptor occupancy of 50% or less, or PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes. 17 - The use as claimed in claim 16, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 2 ng / ml or less or human CNS 5-HT2A receptor occupancy of 40% or less.

18. Use as claimed in claim 16, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 1 ng / ml or less or human CNS 5-HT2A receptor occupancy of 30% or less 19. Use as claimed in claim 16, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 120 minutes.

20. Use as claimed in claim 16, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 180 minutes.

21. The use as claimed in claim 16, wherein the administration of the 5-HT2A agonist substance occurs under conditions that can modulate NMDARs and their subunits in addition to modulating 5-HT2A receptors. 121 22. The use as claimed in claim 16, wherein administration of the 5-HT2A agonist substance can provide protection from excitotoxicity.

23. The use as claimed in claim 16, wherein the administration of the 5-HT2A agonist substance can modulate neurogenesis.

24. The use as claimed in claim 16, wherein the administration of the 5-HT2A agonist substance occurs under conditions effective for the substance to exert neuroplastic effects, including modulation of neural plasticity.

25. Use as claimed in claim 16, wherein the administration of the 5-HT2A agonist substance is repeated for days or months or is chronic.

26. The use as claimed in claim 16, wherein the administration of the 5-HT2A agonist substance is intermittent and occurs every second day, every third day, every third week, every two weeks, or every third month.

27. Use as claimed in claims 5 or 16, wherein the treatment includes metabolic syndrome and its complications. 28.-The use as claimed in claims 5 or 16, wherein the treatment includes impaired glucose tolerance, diabetes and its complication. 29.-The use as claimed in claims 5 or 16, wherein the treatment includes NAFL, NAFLD, NASH and their complications.

30. Use as claimed in claims 5 or 16, where the treatment includes obesity and its complications.

31. Use as claimed in claims 5 or 16, wherein the treatment includes vision impairment and visual loss including macular degeneration and retinopathies.

32. The use as claimed in claims 5 or 16, wherein the treatment includes neurological diseases, including neurodevelopmental and neurodegenerative diseases that may benefit from modulation of neural plasticity, including: Neurological diseases and their symptoms and signs that may respond to neuroplastic drugs and SMSNs include: Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, including mild cognitive impairment associated with aging and chronic disease and its treatment, including chemotherapy, immunotherapy and radiotherapy, Parkinson's disease and related Parkinsonian disorders including but not limited to Parkinson's dementia; disorders associated with the accumulation of beta amyloid protein (including but not limited to cerebrovascular amyloid angiopathy, posterior cortical atrophy);Disorders associated with accumulation or disruption of tau protein and its metabolites, including but not limited to frontotemporal dementia and its variants, frontal variant, primary progressive aphasia (semantic dementia and progressive non-fluent aphasia), corticobasal degeneration, supranuclear palsy; epilepsy; NS trauma; NS infections; NS inflammation, including inflammation from autoimmune disorders, including NMDAR encephalitis, and toxin cytopathology (including microbial toxins, heavy metals, and pesticides, etc.); stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; Fragile X syndrome; Angelman syndrome; hereditary ataxias; neuro-otological and eye movement disorders; neurodegenerative diseases of the retina such as glaucoma, diabetic retinopathy, and age-related macular degeneration; amyotrophic lateral sclerosis; late-onset dyskinesias;hyperkinetic disorders; attention deficit hyperactivity disorder and attention deficit disorders; restless legs syndrome; Tourette syndrome; schizophrenia; autism spectrum disorders; tuberous sclerosis; Rett syndrome; cerebral palsy; reward system disorders including eating disorders [including anorexia nervosa (AN) and bulimia nervosa (BN); and binge eating disorder (BED), trichotillomania, dermotillomania, nail biting; migraine; fibromyalgia;and peripheral neuropathy of any etiology. Symptoms or manifestations of nervous system disorders that may be treated or prevented by neuroplastic substances and drugs include: a decline, impairment, or abnormality in cognitive abilities, including executive function, attention, cognitive speed, memory, language functions (speech, comprehension, reading, and writing), orientation in space and time, practical skills, ability to perform actions, ability to recognize faces or objects, concentration, and alertness; abnormal movements, including akathisia, bradykinesia, tics, myoclonus, dyskinesias, including dyskinesias related to Huntington's disease, levodopa-induced dyskinesias, and neuroleptic-induced dyskinesias, dystonias, tremors, including essential tremor, and restless leg syndrome; parasomnias, insomnia, disturbed sleep patterns; psychosis; delirium; agitation; headache;motor weakness, spasticity, impaired physical endurance; sensory impairment, including impaired vision and visual field defects, smell, taste, hearing and balance, and dysesthesias; dysautonomia; and ataxia, impaired balance or coordination, tinnitus, neuro-otological and eye movement impairments, neurological symptoms of alcohol withdrawal, including delirium, headache, tremors, hallucinations, hypertension.

33. Use as claimed in claims 5 or 16, wherein the treatment includes psychiatric disorders as defined by DSM-5 and ICD-11, which may benefit from modulation of neural plasticity, including Schizophrenia Spectrum and other psychotic disorders, Bipolar and related disorders, Depressive disorders, Anxiety disorders, Obsessive-compulsive and related disorders, Trauma and stressor-related disorders, Dissociative disorders, somatic symptom and related disorders, Eating and feeding disorders, Elimination disorders, Sleep-wake disorders, Sexual dysfunctions, Gender dysphoria disorder, Disruptive, impulse control, and conduct disorders, substance-related and addictive disorders, Neurocognitive disorders, Personality disorders, Paraphilic disorders.

34. Use as claimed in claims 5 or 16, wherein the treatment includes systemic inflammatory conditions and autoimmune disorders.

35. Use as claimed in claims 5 or 16, wherein the treatment includes aging, senescence and associated deficits, including osteoporosis.

36. The use as claimed in claims 5 or 16, wherein the treatment includes dry eye syndrome.

37. The use as claimed in claims 5 or 16, wherein the treatment includes restless leg syndrome.

38. The use as claimed in claims 5 or 16, wherein the function is chosen from visual, auditory, sense of balance, olfactory, gustatory.

39. Use as claimed in claims 5 or 16, wherein the substance is psilocybin, psilocin, norpsilocin, baeocystin, nor-baeocystin or a mixture thereof.

40. The use as claimed in claim 16, wherein the substance is a modified-release formulation of psilocybin, psilocin, norpsilocin, baeocystin, norbaeocystin or a mixture thereof.

41. The use as claimed in claims 5 or 16, wherein the drug is a combination of at least two drugs, the first drug being selected from 5HT2A agonists, including psilocybin or psilocin or norpsilocin or baeocystin or norbaeocystin at a dose of 0.0124 mg and the second drug being selected from a non-competitive, low-affinity, open-channel NMDAR antagonist, including dextromethorphan, dextromethadone, ketamine and its isomers, memantine, amantadine, noribogaine at a dose of 0.01-50 mg; wherein administration of the combination substance provides synergistic effects or improved safety over the administration of either substance alone.

42. The use as claimed in claims 5 or 16, further comprising the administration of the compound of claims 1 to 4 or the 5-HT2A agonist substance in combination with magnesium, zinc, lithium, and salts thereof; wherein the administration of the combination substance provides synergistic effects or improved safety over the administration of any single substance. 43.- The use as claimed in claims 5 or 16, the method comprises the daily oral administration of mushrooms containing psilocybin or psilocin or baeocystin or extracts thereof.

44. The use of a 5-HT2A agonist derivative, including carbamate derivatives, fluoro derivatives and including nitro derivatives and their deuterated versions including deuterated carbamate derivatives, deuterated fluoro derivatives and including nitro derivatives and deuterated fluoro-nitro derivatives, including compounds of any of claims 1 to 4, in the preparation of a medicament for preventing and treating diseases and conditions in a subject.

45. The use listed in any of claims 5 to 44 wherein the substance is coated with an emetic drug to reduce the potential for abuse of the substance.

46. ​​The use listed in any of claims 5 to 45 wherein the administration of the substance is by oral, buccal, sublingual, rectal, vaginal, nasal, aerosol, transdermal, transmucosal, parenteral (e.g., intravenous, intradermal, subcutaneous, and intramuscular injection), epidural, intrathecal, intraauricular, intraocular, including implanted depot formulations, or topically, including creams, lotions, gels and ointments for the skin or eyes and eye drops.

47. A compound of any of claims 1 to 4 for use in the prevention or treatment of diseases and conditions or for improving functions in patients or subjects, wherein the drug is adapted to be administered at doses, dosages, posology, or formulations devoid of clinically significant psychedelic or psychotomimetic actions or effects, and having clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / ml or less, or human CNS 5-HT2A receptor occupancy of 50% or less, or PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes.

48. The compound for use in accordance with claim 47, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 2 ng / ml or less or human CNS 5-HT2A receptor occupancy of 40% or less. 49.- The compound for use according to claim 47, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 1 ng / ml or less or human CNS 5-HT2A receptor occupancy of 30% or less.

50. The compound to be used in accordance with claim 47, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 120 minutes.

51. The compound for use in accordance with claim 47, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 180 minutes.

52. The compound for use according to claim 47, wherein administration of the compound occurs under conditions that can modulate NMDARs and their subunits in addition to modulating 5-HT2A receptors. croaon / Lznz / q / uili 125 53. The compound for use in accordance with claim 47, wherein administration of the compound can provide protection from excitotoxicity.

54. The compound for use in accordance with claim 47, wherein administration of the compound can modulate neurogenesis.

55. The compound for use according to claim 47, wherein the administration of the compound occurs under conditions effective for the substance to exert neuroplastic effects, including modulation of neural plasticity.

56. The compound for use in accordance with claim 47, wherein the administration of the compound is repeated for days or months or is chronic.

57. The compound for use according to claim 47, wherein the administration of the compound is intermittent and occurs every second day, every third day, every third week, every two weeks, or every third month.

58. A 5-HT2A agonist substance for use in the prevention or treatment of diseases and conditions or to enhance functions in patients or subjects, wherein the 5-HT2A agonist substance is adapted to be administered at doses, dosages, posology, or formulations devoid of clinically significant psychedelic or psychotomimetic actions or effects, and having clinical effects comparable to those exerted by human plasma psilocin Cmax of 4 ng / ml or less, or human CNS 5-HT2A receptor occupancy of 50% or less, or PD effects comparable to those exerted by human plasma psilocin Tmax in excess of 60 minutes.

59. The 5-HT2A agonist substance for use according to claim 58, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 2 ng / ml or less or human CNS 5-HT2A receptor occupancy of 40% or less.

60. The 5-HT2A agonist substance for use according to claim 58, wherein said clinical effects are comparable to those exerted by human plasma psilocin Cmax of 1 ng / ml or less or human CNS 5-HT2A receptor occupancy of 30% or less 61. The 5-HT2A agonist substance for use in accordance with claim 58, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 120 minutes.

62. The 5-HT2A agonist substance for use in accordance with claim 58, wherein said PD effects are comparable to those exerted by the Tmax of human plasma psilocin in excess of 180 minutes.

63. The 5-HT2A agonist substance for use according to claim croaon / Lznz / q / uili 126 58, wherein the administration of the 5-HT2A agonist substance occurs under conditions that can modulate NMDARs and their subunits in addition to modulating 5-HT2A receptors.

64. The 5-HT2A agonist substance for use according to claim 58, wherein administration of the 5-HT2A agonist substance can provide protection from excitotoxicity.

65. The 5-HT2A agonist substance for use according to claim 58, wherein administration of the 5-HT2A agonist substance can modulate neurogenesis.

66. The 5-HT2A agonist substance for use according to claim 58, wherein the administration of the 5-HT2A agonist substance occurs under conditions effective for the substance to exert neuroplastic effects, including modulation of neural plasticity.

67. The 5-HT2A agonist substance for use according to claim 58, wherein the administration of the 5-HT2A agonist substance is repeated for days or months or is chronic.

68. The 5-HT2A agonist substance for use according to claim 58, wherein the administration of the 5-HT2A agonist substance is intermittent and occurs every second day, every third day, every third week, every two weeks, or every third month. 69.- The 5-HT2A agonist substance for use in accordance with claims 47 or 58, wherein the treatment includes metabolic syndrome and its complications.

70. The 5-HT2A agonist substance for use in accordance with claims 47 or 58, wherein the treatment includes impaired glucose tolerance, diabetes and its complication. 71.- The 5-HT2A agonist substance for use in accordance with claims 47 or 58, wherein the treatment includes NAFL, NAFLD, NASH and their complications. 72.- The 5-HT2A agonist substance for use in accordance with claims 47 or 58, wherein the treatment includes obesity and its complications.

73. The 5-HT2A agonist substance for use in accordance with claim 47 or 58, wherein the treatment includes vision impairment and visual loss including macular degeneration and retinopathies.

74. The 5-HT2A agonist substance for use according to claim 47 or 58, wherein the treatment includes neurological diseases, including neurodevelopmental diseases and neurodegenerative diseases that may benefit from modulation of neural plasticity, including: Neurological diseases and their symptoms and signs that may respond to neuroplastic drugs and SMSNs include: Alzheimer's disease; presenile dementia; senile dementia; vascular dementia; Lewy body dementia; cognitive impairment, including mild cognitive impairment associated with aging and chronic disease and its treatment, including chemotherapy, immunotherapy and radiotherapy, Parkinson's disease and related Parkinsonian disorders including but not limited to Parkinson's dementia;Disorders associated with the accumulation of beta-amyloid protein (including but not limited to cerebrovascular amyloid angiopathy, posterior cortical atrophy); disorders associated with the accumulation or disruption of tau protein and its metabolites, including but not limited to frontotemporal dementia and its variants, frontal variant, primary progressive aphasia (semantic dementia and progressive non-fluent aphasia), corticobasal degeneration, supranuclear palsy; epilepsy; spinal cord trauma; spinal cord infections; spinal cord inflammation, including inflammation from autoimmune disorders, including NMDAR encephalitis, and toxin cytopathology (including microbial toxins, heavy metals, and pesticides, etc.); stroke; multiple sclerosis; Huntington's disease; mitochondrial disorders; Fragile X syndrome; Angelman syndrome; hereditary ataxias; neuro-otological and eye movement disorders;Neurodegenerative diseases of the retina such as glaucoma, diabetic retinopathy, and age-related macular degeneration; amyotrophic lateral sclerosis; tardive dyskinesia; hyperkinetic disorders; attention deficit hyperactivity disorder and attention deficit disorders; restless legs syndrome; Tourette syndrome; schizophrenia; autism spectrum disorders; tuberous sclerosis; Rett syndrome; cerebral palsy; disorders of the reward system including eating disorders [including anorexia nervosa (AN) and bulimia nervosa (BN); and binge eating disorder (BED), trichotillomania, dermotillomania, nail biting; migraine; fibromyalgia;and peripheral neuropathy of any etiology. Symptoms or manifestations of nervous system disorders that may be treated or prevented by neuroplastic substances and drugs include: a decline, impairment, or abnormality in cognitive abilities, including executive function, attention, cognitive speed, memory, language functions (speech, comprehension, reading, and writing), orientation in space and time, practical skills, ability to perform actions, ability to recognize faces or objects, concentration, and alertness; abnormal movements, including akathisia, bradykinesia, tics, myoclonus, dyskinesias, including dyskinesias related to Huntington's disease, levodopa-induced dyskinesias, and neuroleptic-induced dyskinesias, dystonias, tremors, including essential tremor, and restless leg syndrome; parasomnias, insomnia, disturbed sleep patterns; psychosis; delirium; agitation; headache;motor weakness, spasticity, impaired physical endurance; sensory impairment, including impaired vision and visual field defects, smell, taste, hearing and balance, and dysesthesias; dysautonomia; and ataxia, impaired balance or coordination, tinnitus, neuro-otological and eye movement impairments, neurological symptoms of alcohol withdrawal, including delirium, headache, tremors, hallucinations, hypertension.

75. The 5-HT2A agonist substance for use according to claim 47 or 58, wherein the treatment includes psychiatric diseases as defined by DSM-5 and ICD-11, which may benefit from modulation of neural plasticity, including Schizophrenia Spectrum and other psychotic disorders, Bipolar and related disorders, Depressive disorders, Anxiety disorders, Obsessive-compulsive and related disorders, Trauma and stressor-related disorders, Dissociative disorders, somatic symptom and related disorders, Eating and feeding disorders, Elimination disorders, Sleep-wake disorders, Sexual dysfunctions, Gender dysphoria disorder, Disruptive, impulse control, and conduct disorders, Substance and adjective-related disorders, Neurocognitive disorders, Personality disorders, Paraphilic disorders.

76. The 5-HT2A agonist substance for use in accordance with claims 47 or 58, wherein the treatment includes systemic inflammatory conditions and autoimmune disorders.

77. The 5-HT2A agonist substance for use in accordance with claim 47 or 58, wherein the treatment includes aging, senescence and associated deficits, including osteoporosis.

78. The 5-HT2A agonist substance for use in accordance with claim 47 or 58, wherein the treatment includes dry eye syndrome. 79.- The 5-HT2A agonist substance for use in accordance with claim 47 or 58, wherein the treatment includes restless leg syndrome.

80. The 5-HT2A agonist substance for use in accordance with claim 47 or 58, wherein the function is selected from visual, auditory, balance sense, olfactory, gustatory.

81. The 5-HT2A agonist substance for use in accordance with claim 47 or 58, wherein the substance is psilocybin, psilocin, norpsilocin, baeocystin, norbaeocystin or a mixture thereof. 82.- The 5-HT2A agonist substance for use according to claim 58, wherein the substance is a modified-release formulation of psilocybin, psilocin, norpsilocin, baeocystin, nor-baeocystin or a mixture thereof.

83. The 5-HT2A agonist substance for use according to claim 47 or 58, wherein the drug is a combination of at least two drugs, the first drug being selected from 5-HT2A agonists, including psilocybin, psilocin, norpsilocin, baeocystin, or norbaeocystin at doses of 0.01-24 mg, and the second drug being selected from a non-competitive, low-affinity, open-channel NMDAR antagonist, including dextromethorphan, dextromethadone, ketamine and its isomers, memantine, amantadine, and noribogaine at doses of 0.01-50 mg; wherein administration of the combination substance provides synergistic effects or improved safety over the administration of either substance alone.

84. The 5-HT2A agonist substance for use according to claims 47 or 58, further comprising the administration of the compound of claims 1 to 4 or the 5-HT2A agonist substance in combination with magnesium, zinc, lithium, and salts thereof; wherein the administration of the combination substance provides synergistic effects or improved safety over the administration of either substance alone.

85. The 5-HT2A agonist substance for use according to claim 47 or 58, comprising the daily oral administration of mushrooms containing psilocybin or psilocin or baeocystin or extracts thereof.

86. A 5-HT2A agonist derivative, including carbamate derivatives, fluoro derivatives and including nitro derivatives and their deuterated versions including deuterated carbamate derivatives, deuterated fluoro derivatives and including nitro derivatives and deuterated fluoro-nitro derivatives, including compounds of any of claims 1 to 4, for use in the prevention and treatment of diseases and conditions in a subject.

87. The 5-HT2A agonist substance for use listed in any of claims 47 to 86 wherein the substance is coated with an emetic drug to reduce the potential for abuse of the substance. 88.- The 5-HT2A agonist substance for use listed in any of claims 47 to 87 wherein the administration of the substance is by oral, buccal, sublingual, rectal, vaginal, nasal, aerosol, transdermal, transmucosal, parenteral (e.g., intravenous, intradermal, subcutaneous, and intramuscular injection), epidural, intrathecal, intraauricular, intraocular, including implanted depot formulations, or topically, including creams, lotions, gels and ointments for the skin or eyes and eye drops.