About

David E. Olson is a Professor in the Department of Chemistry at UC Davis, with a research focus on psychoplastogens—small molecules capable of promoting neural plasticity. His lab studies compounds that have potential for treating neuropsychiatric diseases such as depression, anxiety disorders, and addiction. Olson employs a combination of synthetic chemistry, molecular neurobiology, and behavioral neuropharmacology to understand the mechanisms underlying the effects of psychoplastogens on the nervous system and to develop next-generation neurotherapeutics. His professional achievements include receiving numerous awards such as the Mahoney Institute for Neurosciences Rising Star Award (2023), UC Davis Chancellor’s Fellow (2023), and being named one of the 100 Most Influential People in Psychedelics by Psychedelic Invest (2021). Olson has also been recognized for his mentorship and innovation, including the UC Davis Graduate Studies Distinguished Graduate and Postdoctoral Mentoring Award (2021) and the UC Davis Chancellor’s Innovation Award (2021). His work has contributed significantly to the understanding of psychedelic-induced neuroplasticity, with notable publications in high-impact journals such as Science and Nature. Olson's research elucidates the mechanisms of psychedelic compounds, particularly their activation of intracellular 5-HT2A receptors, and explores their therapeutic potential for neuropsychiatric conditions.

Research topics

• Neuroscience
• Psychology
• Biology
• Biochemistry
• Cell biology
• Pharmacology
• Medicine
• Psychotherapist
• Chemistry
• Clinical psychology

Selected publications

• <i>R</i> -MDDMA is a Safer Analogue of MDMA with Therapeutic Potential

  ACS Chemical Neuroscience · 2026-04-21

  articleSenior authorCorresponding

  Recent clinical evidence suggests that racemic 3,4-methylenedioxymethamphetamine (MDMA) might be useful for treating a range of neuropsychiatric diseases including post-traumatic stress disorder (PTSD) and depression. However, concerns about its abuse potential stemming from its monoamine releasing properties have hampered its clinical development. Thus, safer analogues of racemic MDMA with comparable therapeutic effects are highly desirable. Here, we compare the pharmacological effects of MDMA enantiomers with those of its methylated analogue 3,4-methylenedioxy-N,N-dimethylamphetamine (MDDMA). We found that R-MDDMA did not directly activate 5-HT2B receptors, induce serotonin efflux, produce a head-twitch response, impact body temperature, or induce hyperlocomotion at therapeutically relevant doses. However, it still promoted structural neuroplasticity in cortical neurons, facilitated fear extinction learning, and produced sustained antidepressant-like effects. Taken together, our results suggest that R-MDDMA might be a safer MDMA analogue with similar therapeutic properties.

  PublisherDOI

• Synthesis of Clausenamide Isomers and Evaluation of Their Potential as Cortical Neuroplastogens

  ACS Chemical Neuroscience · 2026-05-06

  articleCorresponding

  Neuroplastogens, small molecules that induce beneficial neuronal growth and plasticity, are a class of compounds emerging as new drugs for treating a range of central nervous system conditions. Clausenamide is a plasticity-promoting natural product isolated from the leaves of Clausena lansium, an evergreen native to Southeast Asia and southern China. Herein, we report an efficient synthesis of this compound by a one-pot, three-component assembly of three of the four contiguous stereogenic centers. This method enabled efficient access to six stereoisomers and one analog, which were evaluated for their ability to induce synaptogenesis in primary cortical cultures using high-content imaging. We observed a range of activities for clausenamide stereoisomers, but in general, the postsynaptic effects of the active compounds were greater than their presynaptic effects. Of the stereoisomers tested, (−)-cis-clausenamide exhibited the highest level of cortical synaptogenesis, with this effect likely being dependent on its ability to act as a 5-HT2AR partial agonist.

  PublisherDOI

• Skeletal editing by iron-catalyzed carbene insertion of trichloromethanes

  Chem · 2026-03-01

  article
  PublisherDOI

• 569. Preclinical Pharmacology of DLX-2270: A Novel, Next Generation, Non-Hallucinogenic Neuroplastogen With the Potential for Treating Schizophrenia

  Biological Psychiatry · 2025-04-09

  article
  PublisherDOI

• Zalsupindole is a Nondissociative, Nonhallucinogenic Neuroplastogen with Therapeutic Effects Comparable to Ketamine and Psychedelics

  ACS Chemical Neuroscience · 2025-10-13 · 6 citations

  articleSenior authorCorresponding

  Many neuropsychiatric conditions, including depression, involve synaptic loss and atrophy of the prefrontal cortex. The rapid regrowth of cortical neurons has been hypothesized to explain the rapid and enduring therapeutic effects of psychedelics and the dissociative anesthetic ketamine. However, safety concerns related to hallucinogenic/dissociative properties have limited the addressable patient population that could potentially be treated with these compounds. Thus, substantial efforts have focused on the development of neuroplastogens─compounds that can produce similar effects on structural and functional neuroplasticity as well as rapid and sustained therapeutic behavioral effects without inducing hallucinations or dissociation. Here, we describe the preclinical pharmacology and efficacy of zalsupindole─the first neuroplastogen to be administered to patients with major depressive disorder. Despite lacking any of the acute cellular and behavioral characteristics of hallucinogenic/dissociative compounds, zalsupindole produced robust effects on structural and functional neuroplasticity in the prefrontal cortex of rats as well as sustained antidepressant-like responses. These effects were comparable to or greater than those of ketamine, psilocybin, and N,N-dimethyltryptamine, suggesting that zalsupindole might represent a safer and more scalable neuroplasticity-promoting compound for treating conditions like depression.

  PublisherDOI

• Indolethylamine <i>N</i>-Methyltransferase Deletion Impacts Mouse Behavior without Disrupting Endogenous Psychedelic Tryptamine Production

  ACS Chemical Neuroscience · 2025-09-28

  articleSenior authorCorresponding

  Exogenously administered psychedelics produce both rapid and long-lasting effects on neuroplasticity and behavior, but it is currently unclear if endogenously produced psychedelics can elicit similar effects. There have been relatively few studies on the role of endogenous psychedelics in health and disease, perhaps owing to the difficulty in quantifying their levels and manipulating their production. Here, we describe highly sensitive mass spectrometry-based analytical methods for quantifying endogenous psychedelics in mice, and we disclose a genetic mouse model lacking indolethylamine N-methyltransferase (INMT), an enzyme believed to play a critical role in the production of endogenous psychedelics and previously characterized as a thioether S-methyltransferase. We found that INMT knockout (KO) does not produce any major abnormalities in reproduction or growth, but it does impact a range of mouse behaviors across several distinct domains. However, INMT KO did not result in an obvious decrease in endogenous psychedelic levels, suggesting that psychedelics might be produced by alternative biosynthetic pathways in rodents.

  PublisherDOI

• 164. PSILOCYBIN DURING THE POSTPARTUM PERIOD INDUCES LONG-LASTING ADVERSE EFFECTS IN BOTH MOTHERS AND OFFSPRING

  The International Journal of Neuropsychopharmacology · 2025-08-01

  articleOpen access

  Abstract Background Peripartum mood disorders (PMDs) are a major public health concern; they present in 20% of birthing parents and are responsible for 1 in 4 maternal deaths in the United States. The psychedelic antidepressant psilocybin (PSI) increases social connectedness, self-compassion, and has strong clinical transdiagnostic efficacy for mental illness – making it a candidate treatment to reduce maternal disconnect, personal shame, and blunted affect seen in peripartum mood disorders (PMDs). Despite phase 2 clinical trials actively recruiting postpartum parents to determine if a novel PSI analogue could address peripartum mood disorders [NCT06342310], to date there remains no clinical nor preclinical data describing the safety of psychedelic use during the postpartum period. Aims &amp; Objectives We aimed to examine the efficacy of psilocybin in a preclinical mouse model of PMD. We further assessed the long-term behavioral consequences of PSI exposure on parous mice and their offspring. Method Our group recently developed a model in C57BL6/J mice that examines social stress and limited resources as factors that interfere with mother-infant infant bonding in the early postpartum period. In this model, limited bedding and repeated exposure to an infanticidal male mouse destabilizes maternal care and triggers prolonged stress-related behaviors that remain even in the absence of a social threat. Using this paradigm, we investigated the effects of a single PSI dose on maternal care behaviors, as well as long-term anxiety- and depressive-like behaviors in a standardized behavioral battery after offspring were weaned two weeks later (N=11-16 mice/group). This was compared to the behaviors of virgin female mice two weeks after a single dose of PSI (N=10 mice/group). Finally, we examined the long-term behavioral consequences of adult male and female mice reared by dams exposed to maternal stress and/or PSI using a standardized test battery of social, emotional and cognitive behaviors (N=7-14 mice/sex/group). Results PMD model-exposed mice displayed dramatically impaired caregiving behavior, maternal withdrawal and avoidance from pups, and increased anxiety-like behaviors – none of which were ameliorated by PSI treatment. In fact, two weeks following injection, PSI-treated dams were more anxious and had increased risk of overall behavioral impairments. This was specific to the postpartum period as, by stark contrast, virgin female mice treated with a single dose of PSI exhibited an anxiolytic phenotype and decreased risk of overall behavioral impairments – consistent with previous descriptions of PSI in the literature. Furthermore, just a single postnatal exposure to PSI through breastmilk increased the risk of behavioral phenotypes related to mood and sociability disorders in both male and female mice when aged to adulthood. Discussion &amp; Conclusions Altogether, these data suggest that while PSI has been consistently shown to be safe and effective for treating depression in the general human patient population, as well as in preclinical models of mental health disorders, the same may not be true for exposure during the postpartum period. PSI may pose a major risk for both parous mums and their offspring, and as such, these data highlight the importance of including lactating females and their offspring in preclinical efficacy and safety testing of drugs aimed to be delivered postpartum.

  PublisherOA PDFDOI

• Isolation of Psychedelic Responsive Neurons Underlying Anxiolytic Behavioral States

  Biological Psychiatry · 2025-04-09

  article
  PublisherDOI

• Toward Translatable Biomarkers of Psychedelic-Induced Neuroplasticity

  American Journal of Psychiatry · 2025-01-01 · 7 citations

  articleOpen access1st authorCorresponding

  Numerous preclinical studies have demonstrated that psychedelics promote the growth of cortical neurons in the prefrontal cortex. However, measuring psychedelic-induced structural plasticity in humans has remained a challenge. New advances in positron emission tomography imaging could facilitate the measurement of synaptic proteins in humans following psychedelic administration. Identifying a translatable biomarker of psychedelic-induced neuroplasticity would enable patient stratification and determination of optimal dosing paradigms while also facilitating the discovery of novel compounds that produce similar effects on structural neuroplasticity.

  PublisherOA PDFDOI

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

  Nature Neuroscience · 2025-08-04 · 22 citations

  articleOpen accessSenior author
  PublisherOA PDFDOI

Recent grants

• Chemical and Molecular Tools for Modulating GPCR Function

  NIH · $1.2M · 2023–2028

• Design, Synthesis, and Evaluation of Neural Plasticity-Promoting Analogs of Iboga and Ergoline Alkaloids

  NIH · $1.8M · 2018–2024

• High-throughput Identification of Non-hallucinogenic Psychoplastogens for Treating Addiction

  NIH · $2.7M · 2022–2027

Frequent coauthors

• Jared T. Shaw

  109 shared

• Kanny K. Wan

  National Center for Advancing Translational Sciences

  57 shared

• Susruta Majumdar

  Washington University in St. Louis

  56 shared

• Jinghua Zhao

  National Institutes of Health

  56 shared

• Alyssa L. Verano

  Dana-Farber Cancer Institute

  56 shared

• Samir A. Ross

  University of Mississippi

  56 shared

• Enas Mohamed

  Beni-Suef University

  56 shared

• Larry E. Overman

  55 shared

Labs

• Olson LabPI

Education

• Postdoctoral Associate, Stanley Center for Psychiatric Research

  Broad Institute of MIT and Harvard

  2015

• Ph.D., Chemistry

  Stanford University

  2011

• B.S., Chemistry and Biology

  Union College

  2006

Awards & honors

• Mahoney Institute for Neurosciences (MINS) Rising Star Award…
• UC Davis Chancellor’s Fellow (2023)
• Delix Therapeutics named one of the 10 start-ups to watch by…
• Delix Therapeutics named one of the top academic spinouts by…
• Sacramento Business Journal's 40 Under 40 (2022)