Potentiating Psilocybin

增强裸盖菇素

• 批准号: 10602394
• 负责人: DAVID E CLIFFEL
• 金额: $ 19.81万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-05 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10602394
• 关键词: Acer; Alder plant; Beta Carbolines; Biochemical; Carbolines; Cessation of life; Chemicals; Chemistry; Chronic; Cities; Clinical Treatment; Development; Disease; Disease model; Dose; Drug Interactions; Fruit; Grain; Grant; Growth; Hallucinogens; Harvest; Heterogeneity; History of Medicine; Human; Humidity; Ingestion; Learning; Legal; Link; Liquid substance; Major Depressive Disorder; Maps; Medicine; Mental Depression; Mental disorders; Migraine; Modeling; Modern Medicine; Monitor; Monoamine Oxidase Inhibitors; Names; Neurons; Paper; Patients; Pharmaceutical Preparations; Physiological; Plants; Policy Maker; Psilocybin; Psychotherapy; Publishing; Reporting; Research; Research Personnel; Resources; Rye cereal; Sampling; Selective Serotonin Reuptake Inhibitor; Serotonergic System; Serotonin; Serotonin Syndrome; Signal Transduction; Spatial Distribution; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stable Isotope Labeling; Structure; Supplementation; Techniques; Technology; Temperature; Testing; Therapeutic Effect; Toxicology; Tryptophan; Variant; Wheat; base; common treatment; comparative; detection method; fungus; high risk; inhibitor therapy; instrument; interest; painful neuropathy; psilocin; psychologic; screening; small molecule; treatment-resistant depression; uptake

PROJECT SUMMARY ABSTRACT Plants and fungi have a long history of medicinal use yet, modern medicine has turned away from plant-based medicinals due to heterogeneity that results in inconsistent and unpredictable dosing. In 2018, psilocybin was granted Breakthrough Therapy Designation for the therapy of treatment-resistant depression. Initial results of psychedelic-assisted psychotherapy using the psilocybin molecule to treat major depressive disorder report sustained relief from chronic conditions after just one treatment—a breakthrough treatment indeed. In our understanding, these studies—and many others investigating psilocybin’s effect on a range of conditions—rely on the psilocybin molecule as the active compound, not Psilocybin Sp.. As this treatment gains support, it’s important to consider the differences between the molecule psilocybin and various Psilocybin species. In 2019 Blei et. al. published an unexpected paper revealing that β- carbolines—monoamine oxidase inhibitors (MAOIs)—are also found in five common Psilocybin sp.. Generally, MAOIs are considered to be counter indicated with Selective Serotonin Reuptake Inhibitors (SSRIs)—common treatments for psychiatric disorders, migraine headaches and neuropathic pain. In fact, patients taking SSRIs have developed serotonin syndrome after ingesting mixtures of serotonergic psychedelics and MAOIs—overwhelming the serotonin system and resulting in death. These counter indications are absent in research that relies exclusively on the psilocybin molecule. It is therefore of critical importance that we understand the chemistry of various psilocybin- containing mushrooms so that clinicians, researchers, policymakers, and the public can make informed decisions. To this end, we propose investigating the β-carboline content in 13 different psilocybin-containing species. (Aim 1), the growth conditions that may vary this content (Aim 2), and their effects on the serotonin system (Aim 3). As city and state legislatures are now legalizing and/or decriminalizing Psilocybin sp., these potential drug interactions represent a high-risk to current SSRI patients. With over 100 different species of psilocybin-containing mushrooms spanning at least six genera, there is a lot to learn as legalization proceeds.

项目摘要 植物和真菌有着悠久的药用历史，然而，现代医学已经背离了 植物为基础的药物，由于异质性，导致不一致和不可预测的 剂量。2018年，裸盖菇素被授予突破性疗法称号，用于治疗 难治性抑郁症迷幻辅助心理治疗的初步结果， 裸盖菇素分子治疗重度抑郁症报告慢性抑郁症持续缓解 一次治疗后就能缓解病情--这确实是一种突破性的治疗方法。据我们所知， 这些研究--以及许多其他研究裸盖菇素对一系列疾病的影响的研究--依赖于 作为活性化合物的裸盖菇素分子，而不是裸盖菇素属。随着治疗效果的提高 支持，重要的是要考虑分子psilocybin和各种 裸盖菇素类。在2019年Blei et.发表了一篇意想不到的论文，揭示了β- 咔啉-单胺氧化酶抑制剂（MAOI）-也存在于五种常见的裸盖菇素中 sp..一般来说，MAOI被认为与选择性5-羟色胺再摄取相反 抑制剂（SSRIs）-精神疾病，偏头痛和 神经性疼痛事实上，服用SSRIs的患者在 能致幻药和单胺氧化酶的混合物--压倒了血清素系统 并导致死亡这些相反的迹象是缺乏在研究中，完全依赖于 裸盖菇素分子因此，我们必须了解 各种含裸盖菇素的蘑菇，使临床医生，研究人员，政策制定者， 公众可以在知情的情况下作出决定。为此，我们建议研究β-咔啉 13种不同含裸盖菇素的物种中的含量。(Aim（1）生长条件， 改变这种含量（目标2），以及它们对血清素系统的影响（目标3）。作为城市和州 立法机构现在正在将裸盖菇素合法化和/或非犯罪化，这些潜在药物 这种相互作用对目前的SSRI患者来说是一种高风险。有超过100种不同的 含有裸盖菇素的蘑菇跨越至少六个属，有很多东西要学， 合法化收益。