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Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimetic dosages and formulations

A compound, dimethyl technology, used in pharmaceutical combinations, chemical instruments and methods, medical preparations containing active ingredients, etc.

Pending Publication Date: 2022-02-08
ARBORMENTIS LLC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

It is worth noting that the doses of esketamine recently approved by the FDA for the treatment of depression are still high enough to cause some degree of hallucinogenic / hallucinogenic effects (dissociative effects) Limited to treatment-resistant depression requiring supervision in a doctor's office

Method used

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  • Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimetic dosages and formulations
  • Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimetic dosages and formulations
  • Compositions and methods of use comprising substances with neural plasticity actions administered at non-psychedelic/psychotomimetic dosages and formulations

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0270] The following clinical observations were made in the Netherlands on individuals self-administering sclerotia of Psilocibeatlantis (magictruffles.com). Psilocybeatlantis is a species containing dimethyl-4-hydroxytryptamine phosphate, dimethyl-4-hydroxytryptamine, monomethyl psilocybin and ω-N-methyl-4-hydroxytryptamine (Guzmán G, Hanlin RT, White C. Another new bluing species of Psilocybe from Georgia, U.S.A. Mycotaxon 2003; 86:179–183).

[0271] It is worth noting that the sale and use of sclerotia-like psychedelic mushrooms is legal in the Netherlands, and the manufacturer of the particular brand and species of sclerotia self-administered by the individual stated that the "psychedelic dose" ingested 15 grams [For the first individual, the intake of CF (1.5 grams) was 1 / 10 of the recommended "psychedelic dose", and the intake of the other two individuals GG and PM (3 grams) was the recommended "psychedelic dose". 1 / 5 of the phantom dose].

[0272] The inventors descri...

Embodiment 2

[0303] Example 2 - In vivo studies

[0304] To date, the scientific literature available in clinical settings (safety and efficacy studies) and experimental settings (in vitro and in vivo experimental settings, including the work of Ly et al., 2018) still focuses on Pulse therapy, expected and intended to produce clinically meaningful psychedelic / hallucinogenic effects (Johnson M1, Richards W, Griffiths R. Human hallucinogen research: guidelines for safety. J Psychopharmacol. 2008 Aug;22(6):603-20). A similar approach (pulse exposure to high concentrations) was used in an experimental trial (Ly et al., 2018) that supports the use of psychedelic doses of 5-HT2A agonists.

[0305] To assess whether repeated chronic low-dose (non-psychedelic / hallucinogenic) administration of 5-HT2A agonists potentially modulates neuroplasticity and / or modulates neuroinflammation, and to assess whether these effects are potentially cytoprotective, and these Whether the effect may lead to a pote...

Embodiment 3

[0358] Example 3 - In vitro studies

[0359] To assess the mechanism of potential therapeutic effects and whether repeated chronic low-dose treatment with 5-HT2A agonists might modulate neuroplasticity and / or modulate neuroinflammation, and to assess whether these effects are potentially cytoprotective, including against excitotoxicity The inventors performed a series of preclinical in vitro experiments targeting inflammatory mediators and, ultimately, whether these effects would lead to potentially clinically meaningful therapeutic effects. These tests were specifically designed to assess the potential therapeutic effect of repeated neuroplastic doses (low concentrations) classified as 5-HT2A agonists.

[0360] 1. Effects of dimethyl-4-hydroxytryptamine and dimethyl-4-hydroxytryptamine carbamate on NMDAR subunits in ARPE19 cells and 5-HT2 receptor subtypes

[0361] suppose :

[0362] The membranes of retinal pigment cells (ARPE-19 cell line) express NMDARs and 5-HT2...

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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 presently disclosed to exert NMDAR modulating effects, administered as modulators of neural plasticity, at non- psychedelic / psychotomimetic dosages, posology and formulations, for treatment of diseases and conditions and for improving functions (neuroplastogens).

Description

[0001] Cross References to Related Applications [0002] This application claims priority and the benefit of the filing dates of U.S. Patent Application No. 62 / 814,929, filed March 7, 2019, and U.S. Patent Application No. 62 / 844,151, filed May 7, 2019, the disclosure of which is Incorporated herein by reference in its entirety. technical field [0003] Aspects of the invention relate to compositions and methods comprising substances that provide neuroplasticity, and administering these substances in non-psychedelic and / or hallucinogenic dosages. Background technique [0004] The following sections are intended to introduce the reader to various aspects of art that may be related to various aspects of the present invention that are described and / or claimed below. The discussion is considered helpful in providing the reader with background information to facilitate a better understanding of various aspects of the invention. Accordingly, it should be understood that these st...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/137A61K45/06
CPCA61K31/137A61K45/06A61K31/4045A61P25/28C07D471/04C07D471/08C07D209/12C07D209/16C07D471/18C07C217/60C07D457/06C07C215/52C07F9/5728A61K2300/00A61K31/48A61K31/55A61P3/00A61P27/02C07D457/02A61P27/10A61P1/16A61P3/10A61K31/13A61K31/135A61K31/485A61K31/675A61K33/00A61K33/06A61K33/30C07D471/06C07D471/22
Inventor 保罗·L·曼佛雷蒂查尔斯·E·因图里西S·德马丁A·马塔雷M·罗兰多G·乔达诺C·洛多维基P·布伦M·帕帕加洛F·福利A·阿利蒙蒂J·斯格里尼亚尼A·卡瓦利
Owner ARBORMENTIS LLC
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