Institute for Psychedelics and Neurotherapeutics

They developed a platform called VESSEL to build artificial nanovesicles displaying individual EV surface proteins, one at a time. By stripping away the usual protein complexity of native vesicles, they could directly test which proteins influence neuronal repair.

Prototyping Minimal Extracellular Vesicle Mimetics Using Cell-Free Synthesis The many surface proteins on extracellular vesicles (EVs) allow them to target recipient cells and modulate cellular responses. Despite their importance, relating surface protein and EV function is challenging due to surface protein heterogeneity. Here, we create a bottom-up, cell-free protein-synthesis platform to engineer artificial nanovesicles (ANVs) that display different EV surface protein domains. The platform is termed VESSEL (Vesicle Engineering Systems using Synthetic Expression and Loading). The surface proteins are selected based on proteomics data of native EVs from placental mesenchymal stem cells (PMSCs). To create VESSEL, we establish a protein anchor based on the bacteria membrane protein Aquaporin-Z. This anchor allows the flexible and cell-free protein synthesis of 39 different EV surface protein domains, each anchoring into more than 108 ANVs per μL. Furthermore, we measure the ANVs using high-fidelity assays, including single-ANV flow cytometry, super-resolution imaging, and vesicle-based ELISA. Next, we show the impact of each EV surface protein on cellular uptake. Specifically, we find that certain EV surface protein domains govern ANV uptake into HEK293FT cells, explaining the variable observations in the field. We discovered new proteins, such as CADM1 and NPTN, that mediate high-efficiency cellular uptake. Additionally, five proteins were selected for our neuroprotection assay, where three proteins were significant in increasing SH-SY5Y neurite growth. Our work demonstrates a high-throughput cell-free synthesis platform for studying surface proteins of EVs. It enables the systematic interrogation of EV’s function as “signalosomes” and facilitates the designing of well-defined EV mimetics to mediate cellular function.

#UCDavisIPN Affiliate Aijun Wang and his team released a new study in @acs.org - Nano highlighting how engineering simplified extracellular vesicle mimetics can help uncover which surface proteins actually drive neuroprotective effects. 1/2

Ketamine high not related to treatment success for people with alcohol use disorder, study finds | King's College London The psychedelic effects recreational users often seek from taking ketamine do not predict the therapeutic benefits for people being treated for alcohol use disorder, according to new research from Kin...

You can also read the KCL press release here: www.kcl.ac.uk/news/ketamin...

The psychoactive effects of repeated ketamine infusions and their mechanistic role in the treatment of alcohol use disorder: Secondary analysis of a randomised controlled trial - PubMed People with alcohol use disorder experience alterations in consciousness from 0.8 mg/kg intravenous ketamine administration. Ketamine's effects appear to be broadly consistent across three repeated infusions. Ketamine-related reductions in alcohol consumption do not appear to be mediated by the acut …

Out of @kingscollegelondon.bsky.social and @exeter.ac.uk comes new evidence that the intensity of the #ketamine “high” doesn’t predict treatment success for people with alcohol use disorder. What seems to matter more are the underlying neurobiological effects, not the subjective experience.

C4d, a high-affinity LilrB2 ligand, is elevated in Alzheimer’s disease and mediates synapse pruning | PNAS Synapse pruning sculpts neural circuits throughout life. The human Leukocyte immunoglobulin-like receptor type B2 (LilrB2)/murine Paired immunoglob...

New research in @pnas.org offers fresh insight into how brain connections are lost in #Alzheimer’s disease. The study finds that C4d, a molecule linked to the immune system, increases with age and Alzheimer’s, and can directly trigger the removal of synapses, the connections between neurons.

State Sen. Jesse Salomon Wants to Bring Ibogaine Therapy to Washington State Sen. Jesse Salomon, Washington's mushrooms legislator, wants to broaden the state's psychedelic horizons with Ibogaine therapy, a drug that supposedly acts as an almost miracle balm for psychic ...

#UCDavisIPN Director @deolsonlab.bsky.social on efforts to bring ibogaine therapy to WA State: The potential for treating #addiction, #PTSD, and #TBI is compelling, but federal legality and limited clinical data remain real barriers. Promising therapies still need rigorous science and safety first.

Psychedelics elicit their effects by 5-HT2A receptor-mediated Gi signalling - Nature Psychedelics and their non-hallucinogenic analogues were compared, revealing that serotonin 2A receptor (5-HT2AR)-mediated Gi signalling is essential for hallucinogenic effect, with the functional mec...

This week in #psychedelic science: A new @natureportfolio.nature.com paper disentangles how psychedelics work at the 5-HT2A receptor. The study shows that Gi signaling drives hallucination-like effects, while Gq signaling underlies therapeutic outcomes.

Read the study:

This work provides a clear structural framework for designing more precise ion-channel therapeutics. These insights are especially relevant for neurological disorders where KCa2.2 modulation holds clinical promise.

Structural basis for the subtype-selectivity of KCa2.2 channel activators - Nature Communications Activators of KCa2.2 channels constitute potential novel treatments for neurologic disorders. Here, authors report cryo-EM structures of activator-bound channels, providing a framework for structure-b...

New in @natureportfolio.nature.com - Communications from #UCDavisIPN Affiliate Heike Wulff: Researchers report the first high-resolution cryo-EM structures explaining how small-molecule activators selectively target the KCa2.2 potassium channel.

Stress & Psilocybin: Effects on Maternal Care & Offspring Development | Danielle Stolzenberg | 270 Neurobiology of maternal care in mammals: hormonal influences, stress effects & a study on psilocybin's unexpected effects during the postpartum period.

#UCDavisIPN affiliate Danielle Stolzenberg spoke with the Mind & Matter podcast about the neurobiology of maternal care and her research on psilocybin exposure during the postpartum period. Check it out!

Creating Hallucination-free, Psychedelic-like Molecules by Shining Light on Life’s Basic Building Blocks UC Davis researchers have developed a new method that uses light to transform amino acids — the building blocks of proteins — into molecules that are similar in structure to psychedelics and mimic the...

Check out the new research from #UCDavisIPN trainees Joseph Beckett and Trey Brasher, introducing a light-driven way to convert amino acids into psychedelic-inspired molecules. These compounds engage the serotonin system and may represent a new class of non-hallucinogenic neurotherapeutics.

2025 Leading Research Achievements | Brain & Behavior Research Foundation We are pleased to present you with the 2025 Leading Research Achievements by BBRF Grantees, Prize Winners & Scientific Council Members.

Congratulations to #UCDavisIPN Affiliate and Brain and Behavior Research Foundation grant recipient Alex Nord and the team behind JRT, a non-hallucinogenic analogue of LSD. Their work has been named one of BBRF’s leading research achievements of 2025.

Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis - Molecular Psychiatry Molecular Psychiatry - Transdiagnostic reduction in cortical choline-containing compounds in anxiety disorders: a 1H-magnetic resonance spectroscopy meta-analysis

#UCDavisIPN affiliate Richard Maddock published a meta-analysis that identified a difference in brain choline levels in people with anxiety versus those without. Maddock's team found that brain choline levels in people with anxiety were 8% lower than their non-anxious peers.

Read the paper here:

Together, the findings highlight a promising new class of serotonin-targeting drugs that may preserve the benefits of psychedelics, such as antidepressant or neuroprotective effects, while minimizing perceptual changes.

These novel compounds resemble known psychedelics, engage the brain’s serotonin system, and show therapeutic potential without triggering hallucinogenic behaviors.

Their work introduces a new method to use UV light to convert simple amino acids—the building blocks of proteins—into previously difficult to access small molecules.

Transforming Amino Acids into Serotonin 5-HT2A Receptor Ligands Using Photochemistry A light-induced cyclization via a radical spin-center shift process that results in the direct functionalization of the indole ring at the C4-position is developed into a practical method for the synt...

#UCDavisIPN Affiliates and Ph.D. students Joseph Beckett and Trey Brasher, together with their research advisor and senior author Mark Mascal, have published new research in the Journal of the American Chemical Society using a light-driven chemical reaction to make psychedelic-inspired molecules.

LSD for anxiety and depression? Some early studies show promise. Researchers are investigating whether the drug could be used in mainstream medicine—with and without its hallucinatory effects.

Check out NatGeo's story on LSD as a treatment for anxiety and #depression. In the piece, #UCDavisIPN Director, @deolsonlab.bsky.social, highlights how JRT, the IPN's non-hallucinogenic #psychedelic analogue of LSD, "could be a game-changer" for expanding access to mental health treatments.

The Transmitter’s Rising Stars of Neuroscience 2025 We recognize the outstanding achievements of 25 neuroscientists who stand to shape the field for years to come.

@thetransmitter.bsky.social named #UCDavisIPN affiliate @doctheagrif.bsky.social and former affiliate @tinakim-neuro.bsky.social as rising stars in the field of #neuroscience for 2025. Read more about their work on voltage gated ion channels and #psychedelic -responsive neurons here:

60. Psychedelics Postpartum

Check out #UCDavisIPN Affiliate Danielle Stolzenberg on @drjodipawluski.bsky.social podcast "Mommy Brain Revisited." Danielle discusses just how much we have to learn about #psychedelics as a treatment for the mental health of new mothers and their offspring too. Listen here:

The buzziest neuroscience papers of 2023, 2024 The field took note of work on brain-computer interfaces for speech, the mechanism of psychedelics, defining hippocampal representations, and more.

#UCDavisIPN Affiliate @baleslab.bsky.social and Directors @deolsonlab.bsky.social and John Gray's teams' works were recognized in @thetransmitter.bsky.social list of the Buzziest Neuroscience Papers. Explore the full list and learn what makes these papers stand out: #Neuroscience #Psychedelics

Attend Cure Addiction Now's forum and webinar to hear directly from leading scientists in the field. There are 3 ways to join - in person, online, or on-demand afterwards! To learn more and register, head to this link: cureaddictionnow.org/the-raw-trut...

Patients in the Delix trial that were given zalsupindole saw a rapid and robust reduction in symptoms of MDD that lasted for 4 weeks or more—long after the drug was cleared from the body. Given the safety profile of zalsupindole, the FDA is even allowing for at home administration in future trials!

We shared earlier this year that zalsupindole, a non-hallucinogenic psychedelic analogue created at @UC Davis by #UCDavisIPN Director @deolsonlab.bsky.social and his team, entered phase1B clinical trials. We are now thrilled to share the results!!

Check out #UCDavisIPN affiliate @manvir.bsky.social on the debut episode of the @mindsovermatters.bsky.social podcast. He explores shamanism’s deep roots across cultures and how various aspects have echoed through modern societies.

The team was able to demonstrate that zalsupindole promotes neuroplasticity similarly to ketamine, DMT, and psilocybin without the hallucinogenic effects. Stay tuned for more updates as this compound progresses through the clinical trial process.

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

Read the latest research from Delix on #zalsupindole, a compound invented at the #UCDavisIPN by director @deolsonlab.bsky.social and his team. Zalsupindole, is a non-dissociative, non-hallucinogenic #psychedelic analogue, and is the first neuroplastogen to be administered to patients with MDD!

Indolethylamine N-Methyltransferase Deletion Impacts Mouse Behavior without Disrupting Endogenous Psychedelic Tryptamine Production 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 ...

Behavioral changes appeared, but endogenous psychedelic levels remained largely unchanged suggesting alternative biosynthetic pathways at work.

This study opens the door to new questions about how the body might naturally produce psychedelic compounds.

Read the full study:

#UCDavisIPN Director @deolsonlab.bsky.social and his team studied mice without INMT, an enzyme long thought to be essential for producing endogenous #psychedelics like DMT. The surprise...?

Psilocybin during the postpartum period induces long-lasting adverse effects in both mothers and offspring - Nature Communications The treatment potential of psilocybin for postpartum depression was investigated in a preclinical mouse model. Here the authors show both acute and long-term effects of psilocybin in mothers and their offspring who were exposed via lactation.

In a new publication from #UCDavisIPN affiliate Danielle Stolzenberg, her team found that postpartum mice given psilocybin showed a long-term increase in anxiety behaviors after a single dose. Even more striking, their offspring experienced similar effects.