Potentiating Psilocybin

增强裸盖菇素

• 批准号: 10354547
• 负责人: DAVID E CLIFFEL
• 金额: $ 23.78万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10354547
• 关键词: Acer; Alder plant; Beta Carbolines; Biochemical; Cessation of life; Chemicals; Chemistry; Chronic; Cities; Clinical Treatment; Development; Disease; Disease model; Dose; Drug Interactions; Fruit; Grain; Grant; Growth; Hallucinogens; Harvest; Heterogeneity; Human; Humidity; Ingestion; Learning; Legal; Link; Liquid substance; Major Depressive Disorder; Maps; Mental Depression; Mental disorders; Migraine; Modeling; Modern Medicine; Monitor; Monoamine Oxidase Inhibitors; Names; Neurons; Paper; Patients; Pharmaceutical Preparations; Physiological; Plants; Psychotherapy; Publishing; Recording of previous events; 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; high risk; inhibitor therapy; instrument; interest; painful neuropathy; plant fungi; 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.

项目概要摘要 植物和真菌具有悠久的药用历史，但现代医学已经不再使用它们 植物性药物由于异质性而导致不一致和不可预测 剂量。 2018年，裸盖菇素被授予突破性疗法认定，用于治疗以下疾病： 难治性抑郁症。使用迷幻剂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持续缓解慢性抑郁症 仅一次治疗后的情况——确实是突破性的治疗。在我们的理解中， 这些研究以及许多其他研究裸盖菇素对一系列条件的影响的研究依赖于 裸盖菇素分子作为活性化合物，而不是裸盖菇素 Sp.。随着这种治疗的进展 支持，重要的是要考虑裸盖菇素分子和各种不同分子之间的差异 裸盖菇素种类。 2019 年，Blei 等人。等人。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 (MAOIs) - 也存在于五种常见的裸盖菇碱中 sp.. 一般来说，MAOIs 被认为与选择性血清素再摄取相反 抑制剂（SSRI）——治疗精神疾病、偏头痛和 神经性疼痛。事实上，服用 SSRIs 的患者在服用 SSRIs 后出现了血清素综合征。 摄入 5-羟色胺能致幻剂和 MAOIs 的混合物——压垮 5-羟色胺系统 并导致死亡。这些相反的迹象在完全依赖于 裸盖菇素分子。因此，了解化学反应至关重要 各种含有裸盖菇素的蘑菇，以便临床医生、研究人员、政策制定者和 公众可以做出明智的决定。为此，我们建议研究β-咔啉 13 种不同的含裸盖菇素物种中的含量。 （目标 1），可能的生长条件 改变该含量（目标 2），及其对血清素系统的影响（目标 3）。作为城市和州 立法机关现在正在将裸盖菇素合法化和/或非刑事化，这些潜在的药物 相互作用对当前 SSRI 患者来说存在高风险。拥有超过100种不同的物种 含有裸盖菇素的蘑菇至少涵盖六个属，有很多东西需要学习 合法化的进展。