A new twist in psychedelic research
A groundbreaking study in Nature Neuroscience has found that a non-hallucinogenic psychedelic analog, called tabernanthalog (TBG), can increase brain plasticity without causing hallucinations. Brain plasticity, often described as the brain’s ability to “rewire” itself, plays a critical role in healing from conditions such as depression, PTSD, and addiction.
Traditionally, classic psychedelics like LSD and psilocybin are powerful “psychoplastogens,” meaning they rapidly promote brain growth and flexibility. However, their hallucinogenic effects can make therapy difficult for some patients, limiting access and raising safety concerns. This is where TBG may offer an exciting alternative.
What is a non-hallucinogenic psychedelic analog?
A non-hallucinogenic psychedelic analog is a compound designed to mimic the brain-healing benefits of psychedelics without the trip. TBG is chemically related to psilocybin and 5-MeO-DMT, but unlike those drugs, it does not appear to trigger hallucinations. Instead, it lightly activates serotonin 2A (5-HT2A) receptors—key proteins involved in mood and perception—without overstimulating them.
This subtle activation seems enough to spark neuroplasticity while avoiding the cascade of events that leads to altered perception. In fact, animal studies showed TBG not only boosted dendritic spine growth (tiny connections between neurons) but also blocked the hallucinogenic responses seen with psychedelics.
How does TBG work in the brain?
The researchers tested TBG using mice and pigs, focusing on how it affected neurons in the prefrontal cortex, a region deeply tied to mood regulation. They found:
- Neuroplasticity boost: TBG increased the density of dendritic spines, supporting stronger and more flexible brain circuits.
- Antidepressant-like effects: Mice treated with TBG showed less immobility in stress tests, suggesting improved mood.
- No hallucinations: Pigs given TBG showed receptor engagement without the head shakes and behaviors linked to psychedelic trips.
Perhaps most surprising, TBG achieved these effects without triggering a “glutamate burst” or immediate early gene activation—two processes long thought to be essential for psychedelic-driven plasticity. This challenges old assumptions and opens new doors for drug design.
Why does this matter for mental health?
The promise of non-hallucinogenic psychedelic analogs like TBG is clear: safer, more accessible treatments. If patients can gain the benefits of enhanced brain plasticity without needing guided psychedelic sessions, more people may be able to access care. This could expand options for those with treatment-resistant depression, PTSD, or substance use disorders.
David Olson, director of the UC Davis Institute for Psychedelics and Neurotherapeutics, explains that the goal is to create “scalable neurotherapeutics” that work broadly without requiring the intense preparation, monitoring, and costs of hallucinogenic-assisted therapy.
What comes next?
While animal studies are promising, TBG has not yet been tested in humans. Researchers caution that it remains uncertain whether the compound is truly free of hallucinogenic effects in people. Human trials will be essential to confirm safety, effectiveness, and the exact balance of receptor activation needed to promote healing without unwanted side effects.
Still, this discovery strengthens the idea that it is possible to separate psychedelic therapy’s healing effects from its hallucinatory ones. If confirmed, non-hallucinogenic psychedelic analogs could mark the beginning of a new era in mental health treatment.
Conclusion
The study of TBG highlights how far psychedelic science has come. By showing that neuroplasticity can be boosted without hallucinations, researchers may be unlocking a safer path forward for millions of people struggling with mental health conditions. The journey from animal studies to clinical use will take time, but the future of psychedelic-inspired medicine looks more promising than ever.
References
- Aarrestad IK, Cameron LP, Fenton EM, et al. (2025). The psychoplastogen tabernanthalog induces neuroplasticity without proximate immediate early gene activation. Nature Neuroscience. Publisher page: https://www.nature.com/articles/s41593-025-02021-1?
- Cameron LP, Tombari RJ, Lu J, et al. (2021). A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature. Publisher page: https://www.nature.com/articles/s41586-020-3008-z