The Anti-Trip: Psychedelics That Rewire Your Brain Without the Hallucinations

A Viral Tweet, a Two-Atom Swap, and a Very Big Claim

A tweet from the science communicator Massimo (@Rainmaker1973) went viral with the claim that researchers at UC Davis had developed a molecule that "literally grows new neural connections in the brain." The treatment, the tweet explained, delivers "the powerful brain-repairing benefits of LSD" without hallucinations, achieved by "simply swapping two atoms."¹

The framing is irresistible. A tiny molecular edit. The good parts of psychedelics without the trip. New brain wiring grown on demand. It is also, in the ways that matter most, both more nuanced and more interesting than the headline version suggests.

The real story spans five years, three distinct molecules, a startup with over $100 million in venture backing, and a fundamental question in neuroscience: can you separate the chemistry of brain repair from the experience of losing your mind? David Olson's laboratory at UC Davis has been building toward an answer since 2018, and the data so far is genuinely compelling. It is also almost entirely from mice.²

I want to walk through all of it: what the molecules are, what they actually do to neurons, which claims the data supports, and where the gap between rodent promise and human proof remains uncomfortably wide.

Three Compounds. One Lab. Zero Trips.

The UC Davis story is not about a single molecule. It is about a platform of non-hallucinogenic compounds, each engineered from a different psychedelic scaffold, each designed to promote neuroplasticity without perceptual distortion. Three compounds matter most.

Tabernanthalog (TBG) came first. Published in Nature in December 2020, TBG is a synthetic analog of ibogaine, the psychoactive compound from the African iboga shrub. Olson's team redesigned the molecule to be water-soluble, non-toxic to the heart, and synthesizable in a single step. In mice, TBG promoted dendritic growth, reduced alcohol self-administration, and reduced heroin-seeking behavior, all without triggering head-twitch responses, the standard rodent proxy for hallucinations.³

JRT is the molecule behind the viral tweet. Named after its synthesizer, Jeremy R. Tuck, JRT is an analog of LSD itself. Published in PNAS in April 2025, the compound was created by swapping the positions of a carbon and a nitrogen atom in LSD's indole ring. This single structural change prevents a critical hydrogen bond from forming with a serine residue deep inside the 5-HT2A serotonin receptor. The result: LSD's neuroplasticity-promoting activity without its hallucinogenic signaling cascade.⁴

Zalsupindole (DLX-001) is the commercial bet. Developed by Delix Therapeutics, the company Olson co-founded in 2019, zalsupindole is an analog of 5-MeO-DMT, the potent psychedelic found in Sonoran Desert toad secretions. Unlike TBG and JRT, zalsupindole has crossed into human trials. A Phase Ib study completed in October 2025 showed measurable antidepressant effects. The FDA has cleared it for Phase II with at-home self-administration, a first for any psychedelic-inspired compound.⁵

What "Grows New Neural Connections" Actually Means

The phrase "grows new neural connections" needs unpacking. It does not mean new neurons are being born. It means existing neurons are sprouting new dendritic spines, the tiny mushroom-shaped protrusions where one neuron receives a signal from another. More spines mean more synaptic contact points. More contact points mean denser, more complex neural circuits.⁶

Depression, PTSD, and chronic stress are associated with the opposite: prefrontal cortex neurons lose dendritic spines. Their arbors simplify. The circuits that regulate mood, decision-making, and emotional processing become sparse and disconnected. Ketamine, the only rapid-acting antidepressant currently in clinical use, works in part by promoting new spine growth. So do psilocybin, LSD, and DMT.⁷

Olson's key insight, published in Science in 2023, was that psychedelics promote neuroplasticity through intracellular 5-HT2A receptors, not only the ones on the cell surface. The molecules slip inside the neuron and activate receptors on internal membranes. This triggers a signaling cascade through TrkB (the BDNF receptor), mTOR (a protein synthesis regulator), and AMPA receptors that ultimately drives structural remodeling of the dendrite.⁸

The hallucinations, by contrast, appear to depend on a different branch of the signaling tree. Full agonists like LSD activate both the neuroplasticity pathway and a rapid glutamate burst that engages cortical circuits responsible for perceptual distortion. Partial agonists like TBG and JRT activate the growth pathway while producing minimal glutamate signaling. A 2025 study in Nature Neuroscience confirmed this dissociation directly: TBG induced robust dendritic spine growth in mouse prefrontal cortex without activating the immediate early genes (Arc, c-fos) that classic psychedelics turn on.⁹

In practical terms, the timeline of structural change matters. BDNF mRNA upregulation begins within one hour of exposure. Early morphological changes appear at four to six hours. Peak dendritic spine formation occurs at 24 to 72 hours. And critically, the new spines persist for weeks to months after the drug is cleared, suggesting a single dose may produce lasting circuit-level changes.¹⁰

This is what makes the field genuinely exciting. Unlike SSRIs, which require daily dosing and weeks to show effect, these compounds appear to produce rapid structural remodeling from a single exposure. Whether that remodeling translates to sustained clinical improvement in humans, however, is a question the mouse data cannot answer.

Two Landmark Preclinical Papers and One Very Early Human Trial

A complementary line of evidence comes from Olson's mechanistic work. A 2023 Science paper demonstrated that psychedelics promote neuroplasticity by activating 5-HT2A receptors inside the cell, not just on the surface, explaining why non-hallucinogenic partial agonists can still drive structural growth.⁸ A 2024 Science paper identified specific neurons in the amygdala that respond to psychedelics to produce anti-anxiety behavioral states, providing a potential circuit-level explanation for therapeutic effects.¹¹

Taken together, the mechanistic story is coherent. The preclinical behavioral data is consistent. The early human signal is encouraging. But I want to be precise about what we do and do not have: we have zero completed Phase II or Phase III randomized controlled trials in humans. The structural neuroplasticity data, however impressive under a microscope, comes entirely from rodent cortex.

82% of Psychedelic Animal Studies Test During the Wrong Circadian Phase

A systematic review posted to bioRxiv in 2025 examined how psychedelic research uses animal models and found troubling patterns. Of the studies analyzed, 82% tested animals during their inactive circadian phase, the equivalent of waking a human at 3 AM to measure their drug response. 100% used injection-based dosing rather than oral administration. 89% housed animals in barren cages, environments known to impair baseline neuroplasticity. And none of the chronic stress models used to simulate depression match the complexity of human depressive disorders.¹²

This does not invalidate the preclinical findings. It contextualizes them. When we see a 46% increase in dendritic spines in mouse prefrontal cortex, we are seeing a real biological effect in a simplified system under artificial conditions. Whether that effect translates to functional improvement in a human brain, with its vastly more complex circuitry and its depression shaped by years of lived experience, remains an open question.

There is also a deeper philosophical challenge. Some researchers argue that the subjective psychedelic experience, the ego dissolution, the emotional processing, the sense of connection, is not a side effect but a core therapeutic mechanism. Robin Carhart-Harris at UCSF and others have published data suggesting that the intensity of the mystical experience during psilocybin therapy correlates with clinical improvement.¹³ If that correlation is causal, then engineering out the trip might also engineer out the cure.

The counterargument, championed by Olson and others, is that structural neuroplasticity alone may be sufficient. The mouse data supports this position: TBG and JRT produce antidepressant-like behavioral changes without any perceptual alteration. But mice cannot report mystical experiences, and the forced swim test is not a diagnostic interview. The question will only be settled by head-to-head clinical trials comparing hallucinogenic and non-hallucinogenic approaches in humans, and those trials do not yet exist.

UC Davis Is Not the Only Lab De-Tripping Psychedelics

Bryan Roth's laboratory at UNC-Chapel Hill published a complementary approach in 2022: using computational screening of billions of virtual compounds to identify ultra-selective 5-HT2A agonists with antidepressant effects and no hallucinations in mice. The work was published in Nature Communications and licensed to Onsero, a startup attempting to advance the compounds toward clinical trials.¹⁴

The broader competitive landscape includes companies pursuing supervised psychedelic therapy with hallucinogenic compounds: Compass Pathways (psilocybin for treatment-resistant depression, Phase III), MindMed (LSD microdosing), and the now-rebranded Lykos Therapeutics, whose MDMA-assisted therapy for PTSD was rejected by the FDA in 2024 despite showing 71% remission rates, largely due to concerns about blinding integrity and trial design.¹³

Olson's advantage is breadth. His lab has published non-hallucinogenic analogs from three separate psychedelic scaffolds (ibogaine, LSD, 5-MeO-DMT), each with consistent neuroplasticity data. And Delix is the only company in the space with FDA-cleared at-home dosing for a Phase II trial, a regulatory milestone that, if the efficacy data holds, could make non-hallucinogenic psychoplastogens far more commercially scalable than supervised psychedelic therapy.

The scalability argument matters. A psilocybin therapy session requires 6 to 8 hours of supervised clinical time, a specially trained therapist, a controlled environment, and follow-up integration sessions. Zalsupindole, if Phase II succeeds, could be a pill you take at home. The cost implications are transformative. The question is whether the clinical outcomes are comparable.

Credible Science. Early-Stage Evidence. Watch Closely.