{"id":21627,"date":"2025-04-15T09:33:10","date_gmt":"2025-04-15T09:33:10","guid":{"rendered":"https:\/\/www.europesays.com\/uk\/21627\/"},"modified":"2025-04-15T09:33:10","modified_gmt":"2025-04-15T09:33:10","slug":"lsd-inspired-drug-reverses-psychosis-brain-damage-without-hallucinations","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/uk\/21627\/","title":{"rendered":"LSD-Inspired Drug Reverses Psychosis Brain Damage Without Hallucinations"},"content":{"rendered":"<p><strong>Summary: <\/strong>A new LSD-derived compound called JRT shows promise for treating schizophrenia and other brain disorders without inducing hallucinations. Developed by researchers who altered just two atoms in LSD\u2019s structure, JRT maintains the psychedelic\u2019s neuroplastic effects while avoiding its psychosis-linked risks.<\/p>\n<p>In mouse models, JRT enhanced synaptic growth, boosted antidepressant effects, and improved cognitive flexibility\u2014key challenges in schizophrenia treatment. These findings support the idea that psychedelics can be safely reengineered to unlock brain repair without perceptual side effects.<\/p>\n<p><strong>Key Facts:<\/strong><\/p>\n<ul class=\"wp-block-list\">\n<li><strong>Enhanced Neuroplasticity:<\/strong> JRT increased dendritic spine density by 46% and synapse density by 18%.<\/li>\n<li><strong>No Hallucinogenic Effects:<\/strong> Unlike LSD, JRT did not produce hallucinogenic behavior or schizophrenia-linked gene expression in mice.<\/li>\n<li><strong>Potent Antidepressant:<\/strong> JRT demonstrated antidepressant effects 100 times more potent than ketamine.<\/li>\n<\/ul>\n<p><strong>Source: <\/strong>UC Davis<\/p>\n<p><strong>University of California, Davis researchers have developed a new, neuroplasticity-promoting drug closely related to LSD that harnesses the psychedelic\u2019s therapeutic power with reduced hallucinogenic potential.<\/strong><\/p>\n<p>The research, published in\u00a0Proceedings of the National Academy of Sciences,\u00a0highlights the new drug\u2019s potential as a treatment option for conditions like schizophrenia, where psychedelics are not prescribed for safety reasons.<\/p>\n<p>The compound also may be useful for treating other neuropsychiatric and neurodegenerative diseases characterized by synaptic loss and brain atrophy.<\/p>\n<p>  <img fetchpriority=\"high\" decoding=\"async\" width=\"1200\" height=\"801\" src=\"https:\/\/www.europesays.com\/uk\/wp-content\/uploads\/2025\/04\/psychosis-psychopharmacology-neurosicence.jpg\" alt=\"This shows a head and neurons.\"  \/> JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia, without exacerbating behaviors and gene expression associated with psychosis. Credit: Neuroscience News<\/p>\n<p>To design the drug, dubbed JRT, researchers flipped the position of just two atoms in LSD\u2019s molecular structure.<\/p>\n<p>The chemical flip reduced JRT\u2019s hallucinogenic potential while maintaining its neurotherapeutic properties, including its ability to spur neuronal growth and repair damaged neuronal connections that are often observed in the brains of those with neuropsychiatric and neurodegenerative diseases.<\/p>\n<p>\u201cBasically, what we did here is a tire rotation,\u201d said corresponding author David E. Olson, director of the\u00a0Institute for Psychedelics and Neurotherapeutics\u00a0and a professor of chemistry, and biochemistry and molecular medicine at UC Davis.<\/p>\n<p>\u201cBy just transposing two atoms in LSD, we significantly improved JRT\u2019s selectivity profile and reduced its hallucinogenic potential.\u201d<\/p>\n<p>JRT exhibited powerful neuroplastic effects and improved measures in mice relevant to the negative and cognitive symptoms of schizophrenia, without exacerbating behaviors and gene expression associated with psychosis.<\/p>\n<p>\u201cNo one really wants to give a hallucinogenic molecule like LSD to a patient with schizophrenia,\u201d said Olson, who is also co-founder and chief innovation officer of Delix Therapeutics, a company that aims to bring neuroplastogens to the market.<\/p>\n<p>\u201cThe development of JRT emphasizes that we can use psychedelics like LSD as starting points to make better medicines. We may be able to create medications that can be used in patient populations where psychedelic use is precluded.\u201d<\/p>\n<p><strong>Testing JRT\u2019s potential<\/strong><\/p>\n<p>Olson said that it took his team nearly five years to complete the 12-step synthesis process to produce JRT. The molecule was named after Jeremy R. Tuck, a former graduate student in Olson\u2019s laboratory, who was the first to synthesize it and is a co-first author of the study along with Lee E. Dunlap, another former graduate student in Olson\u2019s laboratory.<\/p>\n<p>Following JRT\u2019s successful synthesis, the researchers conducted a battery of cellular and mouse assays that demonstrated the drug\u2019s neuroplastic effects and improved safety profile relative to LSD.<\/p>\n<p>Key findings included:<\/p>\n<ul class=\"wp-block-list\">\n<li>JRT and LSD have the exact same molecular weight and overall shape, but distinct pharmacological properties.<\/li>\n<li>JRT is very potent and highly selective for binding to serotonin receptors, specifically 5-HT2A receptors, the activation of which are key to promoting cortical neuron growth.<\/li>\n<li>JRT promoted neuroplasticity, or growth between cellular connections in the brain, leading to a 46% increase in dendritic spine density and an 18% increase in synapse density in the prefrontal cortex.<\/li>\n<li>JRT did not produce hallucinogenic-like behaviors that are typically seen when mice are dosed with LSD.<\/li>\n<li>JRT did not promote gene expression associated with schizophrenia. Such gene expression is typically amplified with LSD use.<\/li>\n<li>JRT produced robust anti-depressant effects, with it being around 100-fold more potent than ketamine, the state-of-the-art fast-acting anti-depressant.<\/li>\n<li>JRT promoted cognitive flexibility, successfully addressing deficits in reversal learning that are associated with schizophrenia.<\/li>\n<\/ul>\n<p>\u201cJRT has extremely high therapeutic potential. Right now, we are testing it in other disease models, improving its synthesis, and creating new analogues of JRT that might be even better,\u201d Olson said.<\/p>\n<p><strong>A more effective treatment for schizophrenia<\/strong><\/p>\n<p>Olson emphasized JRT\u2019s potential for treating the negative and cognitive symptoms of schizophrenia, as most current treatments produce limited effects on anhedonia \u2014 the inability to feel pleasure \u2014 and cognitive function.<\/p>\n<p>Clozapine is the one exception, but it has side effects, and is not first-line drug of choice for people severely afflicted with schizophrenia.<\/p>\n<p>Olson and his team are currently testing JRT\u2019s potential against other neurodegenerative and neuropsychiatric diseases.<\/p>\n<p>Additional coauthors include Yara A. Khatib, Cassandra J. Hatzipantelis, Sammy Weiser Novak, Rachel M. Rahn, Alexis R. Davis, Adam Mosswood, Anna M. M. Vernier, Ethan M. Fenton, Isak K. Aarrestad, Robert J. Tombari, Samuel J. Carter, Zachary Deane, Yuning Wang, Arlo Sheridan, Monica A. Gonzalez, Arabo A. Avanes, Noel A. Powell,\u00a0Milan Chytil, Sharon Engel, James C. Fettinger, Amaya R. Jenkins, William A. Carlezon Jr., Alex S. Nord, Brian D. Kangas, Kurt Rasmussen,\u00a0Conor Liston and Uri Manor.<\/p>\n<p><strong>Funding: <\/strong>The research reported on here was funded by grants from the National Institutes of Health, the UC Davis Provost\u2019s Undergraduate Fellowship, the Camille and Henry Dreyfus Foundation, the Dr. Mohsen Najafi Research Award in Medicinal Chemistry, the Boone Family Foundation, Hope for Depression Research Foundation, the Pritzker Neuropsychiatric Disorders Research Consortium, the L.I.F.E. Foundation, the Chan-Zuckerberg Initiative Imaging Scientist Award, and\u00a0a National Science Foundation\u00a0NeuroNex Award.<\/p>\n<p>About this psychopharmacology research news<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Author: <\/strong><a href=\"http:\/\/neurosciencenews.com\/cdn-cgi\/l\/email-protection#51303937343d3d11243235302738227f343524\" target=\"_blank\" rel=\"noreferrer noopener\">Andrew Fell<\/a><br \/><strong>Source: <\/strong><a href=\"https:\/\/ucdavis.edu\" target=\"_blank\" rel=\"noreferrer noopener\">UC Davis<\/a><br \/><strong>Contact: <\/strong>Andrew Fell \u2013 UC Davis<br \/><strong>Image: <\/strong>The image is credited to Neuroscience News<\/p>\n<p class=\"has-background\" style=\"background-color:#ffffe8\"><strong>Original Research: <\/strong>Open access.<br \/>\u201c<a href=\"https:\/\/doi.org\/10.1073\/pnas.2416106122\" target=\"_blank\" rel=\"noreferrer noopener\">Molecular Design of a Therapeutic LSD Analogue with Reduced Hallucinogenic Potential<\/a>\u201d by David E. Olson et al. PNAS<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>Molecular Design of a Therapeutic LSD Analogue with Reduced Hallucinogenic Potential<\/strong><\/p>\n<p>Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ).<\/p>\n<p>Psychedelics possess a remarkable ability to promote cortical neuron growth and increase spine density; however, these compounds are contraindicated for patients with SCZ or a family history of psychosis.<\/p>\n<p>Here, we report the molecular design and de novo total synthesis of (+)-JRT, a structural analogue of lysergic acid diethylamide (LSD) with lower hallucinogenic potential and potent neuroplasticity-promoting properties.<\/p>\n<p>In addition to promoting spinogenesis in the cortex, (+)-JRT produces therapeutic effects in behavioral assays relevant to depression and cognition without exacerbating behavioral and gene expression signatures relevant to psychosis.<\/p>\n<p>This work underscores the potential of nonhallucinogenic psychoplastogens for treating diseases where the use of psychedelics presents significant safety concerns.<\/p>\n","protected":false},"excerpt":{"rendered":"Summary: A new LSD-derived compound called JRT shows promise for treating schizophrenia and other brain disorders without inducing&hellip;\n","protected":false},"author":2,"featured_media":21628,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11],"tags":[215,12385,105,13968,13969,218,219,220,13970,222,13971,12386,4768,13972,16,15],"class_list":{"0":"post-21627","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-brain-research","9":"tag-hallucinations","10":"tag-health","11":"tag-jrt","12":"tag-lsd","13":"tag-mental-health","14":"tag-neurobiology","15":"tag-neuroscience","16":"tag-psychedelics","17":"tag-psychology","18":"tag-psychopharmacology","19":"tag-psychosis","20":"tag-schizophrenia","21":"tag-uc-davis","22":"tag-uk","23":"tag-united-kingdom"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@uk\/114341295312053049","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/21627","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/comments?post=21627"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/posts\/21627\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media\/21628"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/media?parent=21627"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/categories?post=21627"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/uk\/wp-json\/wp\/v2\/tags?post=21627"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}