The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation.

BeobachtungsstudiePubMed4. September 2025PMID: 40760185 DOI

Abstract

Nonhallucinogenic psychoplastogens, such as tabernanthalog (TBG), are being developed as potentially safer, more scalable alternatives to psychedelics for promoting neuronal growth and treating various brain conditions. Currently, it is unclear whether 5-hydroxytryptamine 2A (5-HT2A) receptors and immediate early gene (IEG) activation have a role in the neuroplasticity-promoting effects of nonhallucinogenic psychoplastogens. Here, we use pharmacological and genetic tools in rodents to show that nonhallucinogenic psychoplastogens promote cortical neuroplasticity through the same biochemical pathway-involving 5-HT2A, TrkB, mTOR and AMPA receptor activation-as classic psychedelics and that TBG-induced cortical spinogenesis is required for the sustained antidepressant-like behavioral effect of TBG. In contrast to psychedelics, TBG does not induce an immediate glutamate burst or IEG activation. As these effects have been assumed to be necessary for psychedelic-induced neuroplasticity, our results shed light on the mechanisms by which certain psychoplastogens can promote cortical neuroplasticity in the absence of hallucinogenic effects.

Autoren (38)

LeadNeuroscience Graduate Program, University of California, Davis, Davis, CA, USA.

Neuroscience Graduate Program, University of California, Davis, Davis, CA, USA.

Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Seona D PatelDepartment of Chemistry, University of California, Davis, Davis, CA, USA.

Rohini SambyalDepartment of Chemistry, University of California, Davis, Davis, CA, USA.

Shane B JohnsonDepartment of Psychiatry and Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.

Calvin LyDepartment of Chemistry, University of California, Davis, Davis, CA, USA.

Jayashri ViswanathanDepartment of Chemistry, University of California, Davis, Davis, CA, USA.

Eden V BarraganNeuroscience Graduate Program, University of California, Davis, Davis, CA, USA.

Stephanie A LozanoNeuroscience Graduate Program, University of California, Davis, Davis, CA, USA.

Nicolas SebanNeuroscience Graduate Program, University of California, Davis, Davis, CA, USA.

Hongru HuIntegrative Genetics and Genomics Graduate Program, University of California, Davis, Davis, CA, USA.

Noel A PowellDelix Therapeutics, Inc., Bedford, MA, USA.

Milan ChytilDelix Therapeutics, Inc., Bedford, MA, USA.

Retsina MeyerDelix Therapeutics, Inc., Bedford, MA, USA.

David RoseExpressive Neuroscience, LLC, Syracuse, NY, USA.

Chris HempelExpressive Neuroscience, LLC, Syracuse, NY, USA.

Eric OlsonExpressive Neuroscience, LLC, Syracuse, NY, USA.

Hanne D HansenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Clara A MadsenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Gitte M KnudsenNeurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Chase ReddTranslucence Biosystems, Inc., Irvine, CA, USA.

Damian G WheelerTranslucence Biosystems, Inc., Irvine, CA, USA.

Nathaniel GuanzonTranslucence Biosystems, Inc., Irvine, CA, USA.

Jessie MuirCenter for Neuroscience, University of California, Davis, Davis, CA, USA.

Joseph J HennesseyDepartment of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.

Gerald QuonDepartment of Molecular and Cellular Biology, University of California, Davis, Davis, CA, USA.

John D McCorvyDepartment of Cell Biology, Neurobiology and Anatomy, Neuroscience Research Center and Cancer Center, Medical College of Wisconsin, Milwaukee, WI, USA.

Sunil P GandhiTranslucence Biosystems, Inc., Irvine, CA, USA.

Kurt RasmussenDelix Therapeutics, Inc., Bedford, MA, USA.

Conor ListonDepartment of Psychiatry and Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.

John A GrayInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, Davis, CA, USA.

Boris D HeifetsDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.

Alex S NordInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, Davis, CA, USA.

Christina K KimInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, Davis, CA, USA.

David E OlsonInstitute for Psychedelics and Neurotherapeutics, University of California, Davis, Davis, CA, USA. deolson@ucdavis.edu.

MeSH Terms

AnimalsNeuronal PlasticityMiceGenes, Immediate-EarlyHallucinogensMaleReceptor, Serotonin, 5-HT2ARatsTOR Serine-Threonine KinasesMice, Inbred C57BLReceptor, trkBReceptors, AMPA

Metadaten

StudientypBeobachtungsstudie

QuellePubMed

Publikationsdatum4. September 2025

Zitierungen0

Externe Links

PAuf PubMed ansehen DDOI aufrufen

Studie zitieren

X LinkedIn Email

Auf dem Laufenden bleiben