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They shone ultraviolet light on those molecules and gathered what came out. Something in that harvest behaved in a way nobody expected.<\/p>\n
Hunting new structures<\/p>\n
The work comes from the University of California, Davis (UC Davis<\/a>), where Joseph Beckett, a Ph.D. student in chemistry, has been chasing a simple question.<\/p>\n \u201cThe question that we were trying to answer was, \u2018Is there a whole new class of drugs in this field that hasn\u2019t been discovered?’\u201d Beckett said.<\/p>\n Most psychedelic-inspired drug design starts with an existing molecule \u2013 such as psilocybin or LSD \u2013 and tweaks the edges. <\/p>\n Beckett and his colleague Trey Brasher wanted something with no precedent. No borrowed structure. No existing scaffold to reverse-engineer.<\/p>\n Built with light<\/p>\n To make new candidates, the team turned to amino acids, the building blocks of proteins. They paired several with tryptamine, a small molecule the body produces from the amino acid tryptophan. Then they shone ultraviolet light on the mixtures.<\/p>\n That light triggered chemical changes, breaking and rebuilding bonds to produce entirely new structures. Each compound carried features no chemist had drawn on paper before.<\/p>\n The whole method used common starting materials and a single bench-top light source. Cleaner and faster than the reactions most drug-discovery pipelines rely on.<\/p>\n Picking five winners<\/p>\n Out of the resulting library, the team modeled how strongly 100 of the compounds would bind to the brain\u2019s serotonin receptor \u2013 the same one activated by classical psychedelics<\/a>.<\/p>\n Earlier research<\/a> places this receptor at the center of the brain plasticity effects that may underlie the therapeutic benefits of psychedelics in conditions like depression.<\/p>\n Five of the modeled candidates looked strong enough for laboratory testing. How strongly they activated the receptor ranged from about 60% to over 90 percent.<\/p>\n The top compound drove the receptor to its maximum possible response \u2013 the same ceiling classical psychedelics hit. The team gave that compound a label: D5.<\/p>\n The mice stayed still<\/p>\n Standard pharmacology says a full agonist of that receptor should make a mouse twitch its head \u2013 the field\u2019s shorthand for hallucinogenic-like behavior, used to screen candidates across hundreds of published experiments.<\/p>\n D5 fully activated the receptor, hitting it as hard as a classical psychedelic. The mice didn\u2019t twitch. Not once. The expected behavior simply never appeared.<\/p>\n Not only did the response fail to appear \u2013 D5 actually suppressed twitches that would have happened otherwise. That was the part that stopped the team.<\/p>\n It was a full agonist at the suspected trip-causing receptor, yet it behaved like a non-psychedelic. Until this experiment, no one had reported that combination from a brand-new chemical scaffold.<\/p>\n No known chemical relative<\/p>\n That distinction is what makes the find significant. Other groups have built modified versions of known psychedelics that drop the hallucinations. <\/p>\n A recent paper,<\/a> for example, took that approach with ibogaine, a psychedelic derived from an African shrub, and stripped it down into a simpler, non-hallucinogenic compound.<\/p>\n Those approaches start with an existing molecule and prune it. D5 starts from scratch. Its structure has no direct ancestor among classical psychedelics, which is why Brasher described it as a brand-new therapeutic scaffold.<\/p>\n Brand new is rare in this corner of medicinal chemistry. Most candidates over the past decade have been tweaks and variations on existing themes.<\/p>\n Still a mystery<\/p>\n The team can\u2019t yet explain why D5 fails to make mice twitch. Their working hypothesis is that other serotonin receptors in the brain<\/a> may be dampening the signal that normally produces hallucinations \u2013 canceling it out before it takes hold.<\/p>\n That\u2019s still a guess, not a measurement. What the team plans next is to track which other brain receptors D5 touches.<\/p>\n Researchers hope that work will reveal how each receptor shapes the final effect and where the suppression is actually coming from.<\/p>\n What could change<\/p>\n If the result holds in further animal work, the implications for brain plasticity drugs are real. <\/p>\n That receptor is the same one linked to neuronal growth \u2013 the kind of growth tied to recovery from depression in published clinical trials<\/a>.<\/p>\n A drug that produces those benefits without producing a trip would be easier to dose at home, easier to test broadly, and easier to give to patients who can\u2019t safely take a full-strength psychedelic.<\/p>\n That last group is large. People with a history of psychosis, for example, are excluded from most current trials. A non-hallucinogenic full agonist could change who gets access to this class of drugs.<\/p>\n The work also hands chemists a method. Pairing amino acids with tryptamine and shining ultraviolet light on the mixture is fast, cheap, and built from common ingredients. Other labs can run the same recipe with different inputs and generate their own candidates.<\/p>\n The study is published in the Journal of the American Chemical Society<\/a>.<\/p>\n \u2014\u2013<\/p>\n Like what you read?\u00a0Subscribe to our newsletter\u00a0<\/a>for engaging articles, exclusive content, and the latest updates.<\/p>\n Check us out on\u00a0EarthSnap\u00a0<\/a>, a free app brought to you by\u00a0Eric Ralls\u00a0<\/a>and Earth.com.<\/p>\n \u2014\u2013<\/p>\n","protected":false},"excerpt":{"rendered":"Most drugs designed to work like psychedelics start with one. Chemists take a molecule like psilocybin or LSD,…\n","protected":false},"author":2,"featured_media":455784,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[35],"tags":[163,85,46,522,523],"class_list":["post-455783","post","type-post","status-publish","format-standard","has-post-thumbnail","category-mental-health","tag-health","tag-il","tag-israel","tag-mental-health","tag-mentalhealth"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/455783","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/comments?post=455783"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/posts\/455783\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media\/455784"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/media?parent=455783"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/categories?post=455783"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/il\/wp-json\/wp\/v2\/tags?post=455783"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}