Understanding exactly how psychedelics promote new connections in the brain is critical to developing targeted, non-hallucinogenic therapeutics that can treat neurodegenerative and neuropsychiatric diseases. To achieve this, researchers are mapping the biochemical pathways involved in both neuroplasticity and hallucinations. In new research led by the University of California, Davis, researchers found that non-hallucinogenic versions of psychedelic drugs promote neuroplasticity through the same biochemical pathway as psychedelics. However, unlike psychedelics, they don’t activate genes long thought to be key players in that process. The research, published Aug. 4 in Nature Neuroscience, compared the biochemical pathways activated by the hallucinogenic compound 5-MeO-DMT and its non-hallucinogenic analog tabernanthalog (TBG). “The prevailing hypothesis in the field was that psychedelics promote neuroplasticity by causing this big burst of glutamate in the brain, which then turns on intermediate early genes,” said David E. Olson, director of the Institute for Psychedelics and Neurotherapeutics and a professor of chemistry and of biochemistry and molecular medicine at UC Davis. “We now know that non-hallucinogenic compounds like TBG can promote neuroplasticity without inducing a glutamate burst or immediate early gene activation.” “This work challenges the current dogma in the field,” said John A. Gray, a co-author of the study and the associate director of the Institute for Psychedelics and Neurotherapeutics as well as a professor in the Center for Neuroscience at UC Davis. The team found that TBG promotes neuroplasticity by activating the same psychedelic receptor as 5-MeO-DMT, but the difference is the extent of the activation. The researchers also provide the first direct evidence that a non-hallucinogenic psychedelic analog like TBG, produces sustained antidepressant-like effects through the growth of dendritic spines in the brain’s prefrontal cortex.

Hey everyone, great news from the psychedelic research world! A new Phase 2b study by Beckley Psytech on an intranasal formulation of 5-MeO-DMT (BPL-003) for treatment-resistant depression showed some really positive results. The study found that a single dose of the drug produced rapid and long-lasting antidepressant effects. Participants' depression scores significantly decreased and stayed low for up to 57 days. The drug was also well-tolerated. This is a huge step forward for psychedelic medicine and could lead to a new treatment option for depression. You can read the full article here: https://psychedelicalpha.com/news/beckleys-5-meo-dmt-shows-rapid-durable-antidepressant-effects-in-phase-2b-study

Exploring 5-MeO-DMT as a pharmacological model for deconstructed consciousness