ArticleProceedings of the National Academy of Sciences of the United States of America2025
Molecular design of a therapeutic LSD analogue with reduced hallucinogenic potential.
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Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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Who cites it
22 citing papers in PubMed.
- Deconstruction of lysergic acid diethylamide.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The Emergence of Isotryptamine Analogs as Novel Serotonergic Agents with Psychotherapeutic Potential.ACS pharmacology & translational science · 2026Review
- Psychedelics do not always enhance cognitive flexibility: The potential role of time-varying effects on reward learning processes.Neuroscience and biobehavioral reviews · 2026Review
- Article
- Dissociating the Hallucinogenic and Neuroplastic Effects of Psilocybin.bioRxiv : the preprint server for biology · 2026Article
- Naturally Derived Psilocybin for Therapeutic Use: A Six-Criterion Framework for Evidence, Safety, and Benefit-Risk Considerations in Policy and Clinical Development.Biomolecules · 2026Review
- Probing biomarkers and clinical utility of reward learning across species using the Probabilistic Reward Task: 20 years of findings.Nature. Mental health · 2026Article
- The Emerging Neurobiology of Psychedelics: Critical Periods, Metaplasticity, and Extracellular Matrix Remodeling.Annual review of neuroscience · 2026Review
- Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care.Translational psychiatry · 2026Review
- Characterizing non-hallucinogenic psychedelics beyond the head twitch response: phenotypic fingerprinting of lisuride and LSD.Translational psychiatry · 2026Article
- Article
- AI-derived therapeutic development of a serotonin receptor-targeting drug for the treatment of opioid use disorder.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Correlation networks of blood proteins in the neuroimmunology of schizophrenia-replication and extension.Translational psychiatry · 2026Article
- Ischemia-Induced Neurodegeneration in Glaucoma: Mechanistic Insights and Translational Opportunities for Psychoplastogen-Based Therapies.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Psychedelics: Future Therapeutics in Major Depression?Advances in experimental medicine and biology · 2026Review
- Simple Analogs of the LSD D-Ring: A Consideration of Structure-Activity Relationships and Their Potential as Therapeutics.ACS chemical neuroscience · 2025Review
- Microdosing Psychedelics to Restore Synaptic Density in Schizophrenia.International journal of molecular sciences · 2025Review
- Biased signalingActa pharmaceutica Sinica. B · 2025Review
- The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation.Nature neuroscience · 2025Article
- Psychedelics and the Serotonin Hypothesis of Eating Disorders.Brain sciences · 2025Review
Corrections and comments
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Authors and funding
30 authors.
Jeremy R Tuck *Chemistry and Chemical Biology Graduate Program, University of California, Davis, CA 95616.ORCID 0000-0002-8807-3014
Lee E Dunlap *Chemistry and Chemical Biology Graduate Program, University of California, Davis, CA 95616.
Yara A KhatibInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0000-0002-8342-7100
Cassandra J HatzipantelisInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0000-0001-5376-7887
Sammy Weiser NovakWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037.
Rachel M RahnDepartment of Psychiatry and Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065.
Alexis R DavisChemistry and Chemical Biology Graduate Program, University of California, Davis, CA 95616.
Adam MosswoodInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0009-0008-3842-557X
Anna M M VernierChemistry and Chemical Biology Graduate Program, University of California, Davis, CA 95616.ORCID 0000-0001-7226-4417
Ethan M FentonInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0009-0008-1945-7517
Isak K AarrestadInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.
Robert J TombariChemistry and Chemical Biology Graduate Program, University of California, Davis, CA 95616.ORCID 0000-0002-6561-8181
Samuel J CarterInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0000-0002-2276-4373
Zachary DeaneWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037.ORCID 0009-0009-0223-3290
Yuning WangWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037.
Arlo SheridanWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037.ORCID 0000-0003-2907-2254
Monica A GonzalezInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.
Arabo A AvanesInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0000-0001-6211-7966
Noel A PowellDelix Therapeutics, Inc, Bedford, MA 01730.
Milan ChytilDelix Therapeutics, Inc, Bedford, MA 01730.
Sharon EngelDelix Therapeutics, Inc, Bedford, MA 01730.
James C FettingerDepartment of Chemistry, University of California, Davis, CA 95616.ORCID 0000-0002-6428-4909
Amaya R JenkinsJerry and Phyllis Rappaport Center of Excellence in Basic Neuroscience Research, Harvard Medical School McLean Hospital, Belmont, MA 02478.
William A CarlezonJerry and Phyllis Rappaport Center of Excellence in Basic Neuroscience Research, Harvard Medical School McLean Hospital, Belmont, MA 02478.
Alex S NordInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0000-0003-4259-7514
Brian D KangasJerry and Phyllis Rappaport Center of Excellence in Basic Neuroscience Research, Harvard Medical School McLean Hospital, Belmont, MA 02478.ORCID 0000-0002-4597-9801
Kurt RasmussenDelix Therapeutics, Inc, Bedford, MA 01730.
Conor ListonDepartment of Psychiatry and Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10065.
Uri ManorWaitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037.ORCID 0000-0002-9802-1955
David E OlsonInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, CA 95616.ORCID 0000-0002-4517-0543
Funding
NIEHS Center for Health Effects of AgrochemicalsP30ES005707 · NIEHS · UNIVERSITY OF CALIFORNIA DAVIS · PI PLOPPER, CHARLES GEORGE · 1992 to 2006
$9.9MResearch Project: Pathologic Significance of Maternal AutoantibodiesP50HD103526 · NICHD · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEONARD J. ABBEDUTO, Melissa Dawn Bauman · 2020 to 2026
$9.7MEfficacy of biomarker-guided rTMS for treatment resistant depressionR01MH118388 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI BHATI, MAHENDRA T, GUNNING, FAITH M · 2019 to 2025
$6.2MRegulation of prefrontal cortical circuit function and reward-seeking behavior by stress-induced dendritic spine remodelingR01MH118451 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI Joshua Levitz, Conor M Liston · 2019 to 2026
$5.5MFunctional Elucidation of the Sequence-Encoded Regulatory Activity of Enhancers in Vivo in the BrainR35GM119831 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Alexander Nord · 2016 to 2026
$3.9MImpact of BDNF on the Development of Social Behavior CircuitsR01MH123154 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI LEE, FRANCIS SANG YONG, LISTON, CONOR M · 2020 to 2024
$3.0MPrefrontal Cortical Microcircuit Mechanisms of Working Memory Deficits in Chronic StressR01MH109685 · NIMH · WEILL MEDICAL COLL OF CORNELL UNIV · PI LISTON, CONOR M · 2016 to 2020
$2.8MHigh-throughput Identification of Non-hallucinogenic Psychoplastogens for Treating AddictionR01DA056365 · NIDA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI David E Olson · 2022 to 2026
$2.7MLearning, Memory, and Plasticity (LaMP) Training ProgramT32MH112507 · NIMH · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Karen Zito · 2017 to 2026
$2.4MThe UC Davis enhanced Molecular, Cellular, and Developmental Biology Training ProgramT32GM153586 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI Frederic Louis Chedin, ELVA D DIAZ · 2024 to 2026
$2.3MDesign, Synthesis, and Evaluation of Neural Plasticity-Promoting Analogs of Iboga and Ergoline AlkaloidsR01GM128997 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI OLSON, DAVID E · 2018 to 2022
$1.8MSupplement: Chemical and Molecular Tools for Modulating GPCR FunctionR35GM148182 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI David E Olson · 2023 to 2026
$1.5MBoone Family Foundation N/ACamille and Henry Dreyfus Foundation (Dreyfus Foundation) N/AChan Zuckerberg Initiative (CZI) N/ADelix Therapeutics N/ADr. Mohsen Najafi Research Award in Medicinal Chemistry N/AHHS | National Institutes of Health (NIH) MH109685HHS | National Institutes of Health (NIH) MH114976HHS | National Institutes of Health (NIH) MH118388HHS | National Institutes of Health (NIH) MH118451HHS | National Institutes of Health (NIH) MH123154HHS | National Institutes of Health (NIH) R01DA056365HHS | National Institutes of Health (NIH) R01GM128997HHS | National Institutes of Health (NIH) R35GM119831HHS | National Institutes of Health (NIH) R35GM148182HHS | National Institutes of Health (NIH) T32GM113770HHS | National Institutes of Health (NIH) T32MH112507Hope for Depression Research Foundation (HDRF) N/AL.I.F.E Foundation N/ANICHD NIH HHS P50 HD103526NIDA NIH HHS R01 DA056365NIEHS NIH HHS P30 ES005707NIGMS NIH HHS R01 GM128997NIGMS NIH HHS R35 GM119831NIGMS NIH HHS R35 GM148182NIGMS NIH HHS T32 GM113770NIGMS NIH HHS T32 GM153586NIH HHS S10 OD019980NIH HHS S10 OD025271NIMH NIH HHS R01 MH109685NIMH NIH HHS R01 MH118388NIMH NIH HHS R01 MH118451NIMH NIH HHS R01 MH123154NIMH NIH HHS R56 MH114976NIMH NIH HHS T32 MH112507NSF | Next Generation Network for Neuroscience (NeuroNex) 2014862Pritzker Neuropsychiatric Disorders Research Consortium N/AUniversity of California Davis' Provost's Undergraduate Fellowship N/A
Abstract
Decreased dendritic spine density in the cortex is a key pathological feature of neuropsychiatric diseases including depression, addiction, and schizophrenia (SCZ). 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. 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. 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. This work underscores the potential of nonhallucinogenic psychoplastogens for treating diseases where the use of psychedelics presents significant safety concerns.
Indexed as
Drug DesignHallucinogensLysergic Acid DiethylamideAnimalsDendritic SpinesHumansMiceNeuronal PlasticitySchizophreniaHallucinogensLysergic Acid DiethylamideLSDneuroplasticityneuropsychiatric diseasenonhallucinogenicpsychedelic
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