N<\/em>-dimethyltryptamine or 4-AcO-DMT), a popular gray-market recreational drug, is being studied as an improved alternative to psilocybin as a psilocin prodrug. Psilocybin, which is metabolized into psilocin in the body, is being investigated in clinical trials as a therapeutic for the treatment of substance use disorders, depression, cluster headaches, and various other psychiatric disorders. For treating severe depression, psilocybin in conjunction with psychotherapy has received “Breakthrough Therapy” designation from the FDA, but has not been approved by the FDA for the treatment of any medical condition and remains a DEA Schedule I controlled substance.<\/p>\n\n\n\nWhile psilocybin has garnered the overwhelming majority of attention as \u201cthe active ingredient\u201d in magic mushrooms, other structurally similar tryptamine compounds – which are naturally present in these mushrooms – have largely been ignored as \u201cminor\u201d and unimportant. Characterizing these compounds and comparing them to psilocybin is critical to understanding their role in the psychedelic effects of magic mushrooms and their potential as therapeutics.\u00a0 The authors of the study collaborated to perform comprehensive in vitro<\/em> screens to identify potential biological targets, to asses functional activity at several receptors, and to conduct in vivo<\/em> HTR assays directly comparing naturally occurring tryptamines, active metabolites, and their synthetic analogs.<\/p>\n\n\n\nThe research produced several interesting results pertaining to the structure-activity relationships (SARs) of the studied compounds, the potential roles of the \u201cminor\u201d alkaloids in the psychedelic experience occasioned by magic mushrooms, and the potential for psilacetin (a synthetic psilocin prodrug) to be studied as an improved pharmacological alternative to psilocybin.\u00a0 The SAR findings reported in the paper show that \u201cthe degree of N<\/em>-methylation and 4-position ring substitution can powerfully influence pharmacological effects of psilocybin analogues.\u201d\u00a0 The ability of compounds to induce robust HTR in rodents has been used as a preclinical predictor of potential psychedelic-like activity.\u00a0 Data from the HTR studies indicated that baeocystin and aeruginascin, two naturally occurring magic mushroom tryptamines, do not produce an HTR in mice, indicating that they may not induce psychedelic-like effects in humans on their own.\u00a0\u00a0<\/p>\n\n\n\nNotably, psilacetin, a synthetic psilocybin analog, was found to be more potent than psilocybin <\/strong>in mouse studies. While this result highlights psilacetin\u2019s potential for use as a psilocybin alternative, the authors were careful to qualify their findings by noting that psilacetin \u201cdisplays its own serotonergic receptor activities\u201d in cellular assays. The authors concluded that \u201cfuture studies should directly test the hypothesis that psilacetin is hydrolyzed to psilocin in vivo<\/em>.\u201d <\/p>\n\n\n\n\u201cIt\u2019s an honor to collaborate with the leading scientists in their respective fields to bridge the knowledge gap between psilocybin and these other important compounds,\u201d said Dr. Andrew Chadeayne, CaaMTech CEO. \u201cWe\u2019re drawing closer to a comprehensive understanding of how these compounds act pharmacologically and their potential to be studied as potential treatments for some of the world\u2019s most challenging health conditions.\u201d<\/p>\n","protected":false},"excerpt":{"rendered":"
Researchers directly compared psilocybin with understudied magic mushroom molecules, and synthetic analogs such as psilacetin<\/p>\n","protected":false},"author":5,"featured_media":491,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[5],"tags":[],"acf":[],"_links":{"self":[{"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/posts\/485"}],"collection":[{"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/users\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/comments?post=485"}],"version-history":[{"count":7,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/posts\/485\/revisions"}],"predecessor-version":[{"id":499,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/posts\/485\/revisions\/499"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/media\/491"}],"wp:attachment":[{"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/media?parent=485"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/categories?post=485"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/caam.tech\/wp-json\/wp\/v2\/tags?post=485"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}